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Salsabila S, Khairinisa MA, Wathoni N, Sufiawati I, Mohd Fuad WE, Khairul Ikram NK, Muchtaridi M. In vivo toxicity of chitosan-based nanoparticles: a systematic review. ARTIFICIAL CELLS, NANOMEDICINE, AND BIOTECHNOLOGY 2025; 53:1-15. [PMID: 39924869 DOI: 10.1080/21691401.2025.2462328] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 01/08/2025] [Accepted: 01/27/2025] [Indexed: 02/11/2025]
Abstract
Chitosan nanoparticles have been extensively utilised as polymeric drug carriers in nanoparticles formulations due to their potential to enhance drug delivery, efficacy, and safety. Numerous toxicity studies have been previously conducted to assess the safety profile of chitosan-based nanoparticles. These toxicity studies employed various methodologies, including test animals, interventions, and different routes of administration. This review aims to summarise research on the safety profile of chitosan-based nanoparticles in drug delivery, with a focus on general toxicity tests to determine LD50 and NOAEL values. It can serve as a repository and reference for chitosan-based nanoparticles, facilitating future research and further development of drugs delivery system using chitosan nanoparticles. Publications from 2014 to 2024 were obtained from PubMed, Scopus, Google Scholar, and ScienceDirect, in accordance with the inclusion and exclusion criteria.The ARRIVE 2.0 guidelines were employed to evaluate the quality and risk-of-bias in the in vivo toxicity studies. The results demonstrated favourable toxicity profiles, often exhibiting reduced toxicity compared to free drugs or substances. Acute toxicity studies consistently reported high LD50 values, frequently exceeding 5000 mg/kg body weight, while subacute studies typically revealed no significant adverse effects. Various routes of administration varied, including oral, intravenous, intraperitoneal, inhalation, and topical, each demonstrating promising safety profiles.
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Affiliation(s)
- Shela Salsabila
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, Sumedang, Indonesia
| | - Miski Aghnia Khairinisa
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Sumedang, Indonesia
| | - Nasrul Wathoni
- Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, Indonesia
| | - Irna Sufiawati
- Department of Oral Medicine, Faculty of Dentistry, Universitas Padjadjaran, Sumedang, Indonesia
| | - Wan Ezumi Mohd Fuad
- Programme of Biomedicine, School of Health Sciences, USM Health Campus, Kubang Kerian, Kelantan, Malaysia
| | | | - Muchtaridi Muchtaridi
- Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, Sumedang, Indonesia
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Abo-Zaid MA, Elsapagh RM, Sultan NS, Mawkili W, Hegazy MM, Ismail AH. Allergy Treatment: A Comprehensive Review of Nanoparticle-based Allergen Immunotherapy. FRONT BIOSCI-LANDMRK 2025; 30:26550. [PMID: 40152375 DOI: 10.31083/fbl26550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 11/06/2024] [Accepted: 11/13/2024] [Indexed: 03/29/2025]
Abstract
Allergic disorders rising in prevalence globally, affecting a substantial proportion of individuals in industrialized nations. The imbalance in the immune system, characterized by elevated allergen-specific T helper 2 (Th2) cells and immunoglobulin E (IgE) antibodies, is a key factor in allergy development. Allergen-specific immunotherapy (AIT) is the only treatment capable of alleviating allergic symptoms, preventing new sensitizations, and reducing asthma risk in allergic rhinitis patients. Traditional AIT, however, faces challenges such as frequent administration, adverse effects, and inconsistent patient outcomes. Nanoparticle-based approaches have emerged as a promising strategy to enhance AIT. This review explores the utilization of nanoparticles in AIT, highlighting their ability to interact with the immune system and improve therapeutic outcomes. Various types of nanoparticles, including polyesters, polysaccharide polymers, liposomes, protamine-based nanoparticles (NPs), and polyanhydrides, have been employed as adjuvants or carriers to enhance AIT's efficacy and safety. Nanoparticles offer advantages such as allergen protection, improved immune response modulation, targeted cell delivery, and reduced side effects. This review provides an overview of the current landscape of nanoparticle-based allergen immunotherapy, discussing its potential to revolutionize allergy treatment compared to traditional immunotherapy.
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Affiliation(s)
- Mabrouk A Abo-Zaid
- Department of Biology, College of Science, Jazan University, P.O. Box. 114, 45142 Jazan, Kingdom of Saudi Arabia
| | | | - Nourhan S Sultan
- Biotechnology Department, Faculty of Science, Cairo University, 12613 Giza, Egypt
| | - Wedad Mawkili
- Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, 45142 Jazan, Kingdom of Saudi Arabia
| | - Maysa M Hegazy
- Department of Biology, College of Science, Jazan University, P.O. Box. 114, 45142 Jazan, Kingdom of Saudi Arabia
| | - Ahmed H Ismail
- Department of Biology, College of Science, Jazan University, P.O. Box. 114, 45142 Jazan, Kingdom of Saudi Arabia
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Chaturvedi S, Gaur A, Garg A. Development and optimization of raloxifene hydrochloride loaded lipid nanocapsule based hydrogel for transdermal delivery. Ther Deliv 2025; 16:139-154. [PMID: 39877995 PMCID: PMC11849957 DOI: 10.1080/20415990.2025.2457312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Accepted: 01/20/2025] [Indexed: 01/31/2025] Open
Abstract
AIM Development and optimization of raloxifene hydrochloride loaded lipid nanocapsule hydrogel for transdermal delivery. METHOD A 33 Box-Behnken Design and numerical optimization was performed to obtain the optimized formulation. Subsequently, the optimized raloxifene hydrochloride loaded lipid nanocapsule was developed using phase inversion temperature and characterized for physicochemical properties. Furthermore, the optimized lipid nanocapsule was loaded into a hydrogel and evaluated for rheology, spreadability, ex-vivo skin permeation, deposition and irritation. RESULTS The numerical optimization suggested an optimal formula with desirability value of 0.852 and low prediction errors. The optimized formulation showed good % drug entrapment efficiency (79.56 ± 2.34%), nanometer size (56.68 ± 1.2 nm), monodisperse nature (PDI = 0.176 ± 0.2), spherical morphology and good drug-excipient compatibility. The raloxifene hydrochloride loaded lipid nanocapsule hydrogel showed shear thinning properties, sustained drug delivery, dermal compatibility and significantly higher permeability (2-fold), retention (3.37) for raloxifene hydrochloride compared to the control. CONCLUSION The present study showed a successful development of raloxifene hydrochloride loaded lipid nanocapsule hydrogel with improved skin permeation, retention, and good topical compatibility. This formulation may overcome the challenges associated with raloxifene hydrochloride oral delivery including low bioavailability.
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Affiliation(s)
| | - Arushi Gaur
- Institute of Pharmaceutical Research, GLA University, Mathura, India
| | - Anuj Garg
- Institute of Pharmaceutical Research, GLA University, Mathura, India
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Chavan GS, Belgamwar A, Patil KD, Agrawal YO. Mechanistic Understanding of Onychomycosis Progression and Current Advancement in the Transungual Drug Delivery System. Crit Rev Ther Drug Carrier Syst 2025; 42:89-125. [PMID: 40084518 DOI: 10.1615/critrevtherdrugcarriersyst.2024053869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2025]
Abstract
Onychomycosis, a nail infection prevalent in 50 to 60% of all nail illnesses globally, caused by dermatophytes, poses significant challenges to current therapies due to their limitations in effective administration. This review explores recent advancements in novel drug delivery systems while exploring the molecular mechanisms underlying onychomycosis progression. The physicochemical properties of antifungal treatments and the intricate structure of the nail plate present challenges and can be addressed by nanotechnology-enabled solutions. Furthermore, the review extensively covers diagnostic methods crucial for accurate onychomycosis identification. This review offers insights to enhance onychomycosis management by elucidating mechanistic aspects of the disease. Emphasizing the role of nanotechnology in drug delivery systems, it addresses current treatment challenges using innovative approaches. Moreover, the evaluation of various formulations highlights opportunities to improve therapeutic efficacy. Overall, this comprehensive review explores the current status, challenges, diagnostics advances, and novel approaches for the administration of drugs for the management of onychomycosis.
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Affiliation(s)
- Gaurav S Chavan
- Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule, Maharashtra, India
| | - Aarti Belgamwar
- Shri Vile Parle Kelvani Mandal's Institute of Pharmacy, Dhule
| | - Kiran D Patil
- Shri Vile Parle Kelavani Mandal's Institute of Pharmacy, Dhule
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Vochița G, Cadinoiu AN, Rață DM, Atanase LI, Popa M, Mahdieh A, Mihai CT, Stache AB, Moldovan CV, Băcăiţă ES, Condriuc IP, Gherghel D. Comparative In Vitro Study between Biocompatible Chitosan-Based Magnetic Nanocapsules and Liposome Formulations with Potential Application in Anti-Inflammatory Therapy. Int J Mol Sci 2024; 25:8454. [PMID: 39126023 PMCID: PMC11313677 DOI: 10.3390/ijms25158454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 07/26/2024] [Accepted: 07/31/2024] [Indexed: 08/12/2024] Open
Abstract
This study describes the comparison between the interaction of a series of peptide-functionalized chitosan-based nanocapsules and liposomes with two cell lines, i.e., mouse macrophages RAW 264.7 and human endothelial cells EA.hy926. Both types of nanocarriers are loaded with magnetic nanoparticles and designed for anti-inflammatory therapy. The choice of these magnetic nanostructures is argued based on their advantages in terms of size, morphology, chemical composition, and the multiple possibilities of modifying their surface. Moreover, active targeting might be ensured by using an external magnetic field. To explore the impact of chitosan-based nanocapsules and liposomes on cell cytophysiology, the cell viability, using the MTT assay, and cell morphology were investigated. The results revealed low to moderate cytotoxicity of free nanocapsules and significant cytotoxicity induced by chitosan-coated liposomes loaded with dexamethasone, confirming its release from the delivery system. Thus, after 48 h of treatment with nanocapsules, the viability of RAW 264.7 cells varied between 88.18% (OCNPM-1I, 3.125 µg/mL) and 76.37% (OCNPM-1, 25 µg/mL). In the same conditions, EA.hy926 cell viability was between 99.91% (OCNPM-3, 3.125 µg/mL) and 75.15% (OCNPM-3, 25 µg/mL) at the highest dose (25 µg/mL), the values being comparable for both cell lines. Referring to the cell reactivity after dexamethasone-loaded liposome application, the lowest viability of RAW 264.7 cells was 41.25% (CLDM5CP-1, 25 µg/mL) and 58.20% (CLDMM2CP-1 1.25 µg/mL) in the endothelial cell line, proving a selective character of action of nanocarriers. The cell morphology test, performed to support and confirm the results obtained by the MTT test, revealed a differentiated response for the two types of nano-carriers. As expected, an intense cytotoxic effect in the case of dexamethasone-loaded liposomes and a lack of cytotoxicity for drug-free nanocapsules were noticed. Therefore, our study demonstrated the biocompatible feature of the studied nanocarriers, which highlights them for future research as potential drug delivery systems for pharmacological applications, including anti-inflammatory therapy.
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Affiliation(s)
- Gabriela Vochița
- Institute of Biological Research Iasi, Branch of NIRDBS, 700107 Iasi, Romania; (G.V.); (D.G.)
| | - Anca Niculina Cadinoiu
- Faculty of Medicine, Apollonia University of Iasi, 700511 Iasi, Romania; (A.N.C.); (D.-M.R.); (M.P.)
| | - Delia-Mihaela Rață
- Faculty of Medicine, Apollonia University of Iasi, 700511 Iasi, Romania; (A.N.C.); (D.-M.R.); (M.P.)
| | - Leonard Ionuț Atanase
- Faculty of Medicine, Apollonia University of Iasi, 700511 Iasi, Romania; (A.N.C.); (D.-M.R.); (M.P.)
- Academy of Romanian Scientists, 050045 Bucharest, Romania
| | - Marcel Popa
- Faculty of Medicine, Apollonia University of Iasi, 700511 Iasi, Romania; (A.N.C.); (D.-M.R.); (M.P.)
- Academy of Romanian Scientists, 050045 Bucharest, Romania
| | - Athar Mahdieh
- Department of Pharmaceutics, School of Pharmacy, University of Oslo, Blindern, P.O. Box 1068, N-0316 Oslo, Norway;
| | - Cosmin-Teodor Mihai
- Institute of Biological Research Iasi, Branch of NIRDBS, 700107 Iasi, Romania; (G.V.); (D.G.)
- Praxis Medical Investigations, 700376 Iasi, Romania
| | - Alexandru-Bogdan Stache
- Department of Molecular Genetics, Center for Fundamental Research and Experimental Development in Translational Medicine—TRANSCEND, Regional Institute of Oncology, 700483 Iasi, Romania;
| | - Cristina-Veronica Moldovan
- Department of Biology, Faculty of Biology, Alexandru Ioan Cuza University of Iasi, Bd. Carol I, Nr. 11, 700506 Iasi, Romania
| | - Elena Simona Băcăiţă
- Faculty of Machine Manufacturing and Industrial Management, Gheorghe Asachi Technical University of Iasi, D. Mangeron Bld. No. 73, 700050 Iasi, Romania;
| | - Iustina Petra Condriuc
- Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Daniela Gherghel
- Institute of Biological Research Iasi, Branch of NIRDBS, 700107 Iasi, Romania; (G.V.); (D.G.)
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Sunena, Tomar D, Jawla S. Clinical Applications of Sunscreens and Formulation Advancements. Curr Drug Res Rev 2024; 16:198-208. [PMID: 37464824 DOI: 10.2174/2589977515666230718124841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 05/05/2023] [Accepted: 06/06/2023] [Indexed: 07/20/2023]
Abstract
Sunscreens cover the big market ratio in terms of cosmetic applications, but the therapeutic necessity of sunscreen still needs to be uncovered in the clinical context. Clinically, sunscreens are being employed more often nowadays as a result of the rising consequences of skin malignancies and the photodamaging effects of UV radiation. Sunscreens are essential to prevent aging by shielding the skin from the harmful effects of ultraviolet (UV) radiation. Over the recent decades, there has been a significant evolution in the usage of sunscreens as photo protectants. The demand for sunscreen formulations will inevitably rise as more people become aware of the protection that sunscreens provide against tanning, photoaging, non-melanoma skin cancers, premalignant skin lesions, and skin melanomas. The novel contemporary formulation techniques are also beneficial in enhancing the product's aesthetic look and quality. Recently, regulatory agencies have also started paying attention to the regulation of the clinical application, efficacy, and safety parameters related to sunscreen. This review underlines the pathophysiological response of UV exposure with the therapeutic applications of sunscreen in various dermatological conditions and the recent formulation advancements in the development of sunscreen.
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Affiliation(s)
- Sunena
- Geeta Institute of Pharmacy, Geeta University, Panipat, 132145, India
| | - Deepali Tomar
- Geeta Institute of Pharmacy, Geeta University, Panipat, 132145, India
| | - Sunil Jawla
- Geeta Institute of Pharmacy, Geeta University, Panipat, 132145, India
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Dong C, Yu X, Jin K, Qian J. Overcoming brain barriers through surface-functionalized liposomes for glioblastoma therapy; current status, challenges and future perspective. Nanomedicine (Lond) 2023; 18:2161-2184. [PMID: 38180008 DOI: 10.2217/nnm-2023-0172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2024] Open
Abstract
Glioblastoma (GB) originating from astrocytes is considered a grade IV astrocytoma tumor with severe consequences. The blood-brain barrier (BBB) offers a major obstacle in drug delivery to the brain to overcome GB. The current treatment options possess limited efficacy and maximal systemic toxic effects in GB therapy. Emerging techniques such as targeted drug delivery offer significant advantages, including enhanced drug delivery to the tumor site by overcoming the BBB. This review article focuses on the status of surface-modified lipid nanocarriers with functional ligands to efficiently traverse the BBB and improve brain targeting for successful GB treatment. The difficulties with surface-functionalized liposomes and potential future directions for opening up novel treatment options for GB are highlighted.
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Affiliation(s)
- Changming Dong
- Department of Neurosurgery, Shaoxing People's Hospital, Shaoxing, Zhejiang, 312000, China
| | - Xuebin Yu
- Department of Neurosurgery, Shaoxing People's Hospital, Shaoxing, Zhejiang, 312000, China
| | - Ketao Jin
- Department of Colorectal Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, Zhejiang, 321000, China
| | - Jun Qian
- Department of Colorectal Surgery, Xinchang People's Hospital, Affiliated Xinchang Hospital, Wenzhou Medical University, Xinchang, Zhejiang, 312500, China
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Weng J, Durand A, Desobry S. Chitosan-Based Particulate Carriers: Structure, Production and Corresponding Controlled Release. Pharmaceutics 2023; 15:1455. [PMID: 37242694 PMCID: PMC10221392 DOI: 10.3390/pharmaceutics15051455] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 04/30/2023] [Accepted: 05/04/2023] [Indexed: 05/28/2023] Open
Abstract
The state of the art in the use of chitosan (CS) for preparing particulate carriers for drug delivery applications is reviewed. After evidencing the scientific and commercial potentials of CS, the links between targeted controlled activity, the preparation process and the kinetics of release are detailed, focusing on two types of particulate carriers: matrix particles and capsules. More precisely, the relationship between the size/structure of CS-based particles as multifunctional delivery systems and drug release kinetics (models) is emphasized. The preparation method and conditions greatly influence particle structure and size, which affect release properties. Various techniques available for characterizing particle structural properties and size distribution are reviewed. CS particulate carriers with different structures can achieve various release patterns, including zero-order, multi-pulsed, and pulse-triggered. Mathematical models have an unavoidable role in understanding release mechanisms and their interrelationships. Moreover, models help identify the key structural characteristics, thus saving experimental time. Furthermore, by investigating the close relation between preparation process parameters and particulate structural characteristics as well as their effect on release properties, a novel "on-demand" strategy for the design of drug delivery devices may be developed. This reverse strategy involves designing the production process and the related particles' structure based on the targeted release pattern.
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Affiliation(s)
- Jiaqi Weng
- Université de Lorraine, LIBio, F-54000 Nancy, France;
- Université de Lorraine, CNRS, LCPM, F-54000 Nancy, France;
| | - Alain Durand
- Université de Lorraine, CNRS, LCPM, F-54000 Nancy, France;
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Rosenfeld J, Ganachaud F, Lee D. Modulation of Oil/Polymer Nanocapsule Size via Phase Diagram-Guided Microfluidic Coprecipitation. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2023; 39:5477-5485. [PMID: 37015180 DOI: 10.1021/acs.langmuir.3c00183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/19/2023]
Abstract
Flow-based nanoprecipitation of different solutes via rapid mixing of two miscible liquids is a scalable strategy for manufacturing nanoparticles with various shapes and morphologies. Controlling the size of nanoparticles in flow-based nanoprecipitation, however, is often left to empirical variations in the flow rate ratios or the total flow rate of the two streams. In this work, we investigate the coprecipitations of oil and polymer to form nanocapsules via the Ouzo effect using glass capillary microfluidics across a range of mixing conditions. In the range of flow rates studied, the two streams mix convectively in micro-vortices formed at the junction of the two stream inlets. Using computational fluid dynamics simulations and glass capillary microfluidic nanoprecipitation, we establish a relationship between the precipitation conditions occurring experimentally in situ and the location on the ternary Ouzo phase diagram where precipitation is taking place. We find that a key variable in the resulting average diameter of the fabricated capsules is the degree of supersaturation experienced by both the oil and the polymer in the vortex zone of the device, showing a strong correlation between the two values. The control over the nanocapsule size by varying the extent of supersaturation of both precipitants is demonstrated by using two oils having distinct phase diagrams. This work provides a systematic approach to controlling the size of nanoparticles fabricated via continuous nanoprecipitation by linking the in situ flow conditions to ternary phase diagram behavior, enabling accurate control over nanocapsule size.
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Affiliation(s)
- Joseph Rosenfeld
- Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
| | - Francois Ganachaud
- Complex Assemblies of Soft Matter, UMI 3254, Solvay/CNRS/UPenn, 350 George Patterson Boulevard, Bristol, Pennsylvania 19007, United States
- Université de Lyon, CNRS, Université Claude Bernard Lyon 1, INSA-Lyon, Université Jean Monnet, UMR5223, Ingénierie des Matériaux Polymères, F69621 Villeurbanne Cedex, France
| | - Daeyeon Lee
- Department of Chemical and Biomolecular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
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Graván P, Aguilera-Garrido A, Marchal JA, Navarro-Marchal SA, Galisteo-González F. Lipid-core nanoparticles: Classification, preparation methods, routes of administration and recent advances in cancer treatment. Adv Colloid Interface Sci 2023; 314:102871. [PMID: 36958181 DOI: 10.1016/j.cis.2023.102871] [Citation(s) in RCA: 25] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 02/03/2023] [Accepted: 03/06/2023] [Indexed: 03/11/2023]
Abstract
Nanotechnological drug delivery platforms represent a new paradigm for cancer therapeutics as they improve the pharmacokinetic profile and distribution of chemotherapeutic agents over conventional formulations. Among nanoparticles, lipid-based nanoplatforms possessing a lipid core, that is, lipid-core nanoparticles (LCNPs), have gained increasing interest due to lipid properties such as high solubilizing potential, versatility, biocompatibility, and biodegradability. However, due to the wide spectrum of morphologies and types of LCNPs, there is a lack of consensus regarding their terminology and classification. According to the current state-of-the-art in this critical review, LCNPs are defined and classified based on the state of their lipidic components in liquid lipid nanoparticles (LLNs). These include lipid nanoemulsions (LNEs) and lipid nanocapsules (LNCs), solid lipid nanoparticles (SLNs) and nanostructured lipid nanocarriers (NLCs). In addition, we present a comprehensive and comparative description of the methods employed for their preparation, routes of administration and the fundamental role of physicochemical properties of LCNPs for efficient antitumoral drug-delivery application. Market available LCNPs, clinical trials and preclinical in vivo studies of promising LCNPs as potential treatments for different cancer pathologies are summarized.
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Affiliation(s)
- Pablo Graván
- Department of Applied Physics, Faculty of Science, University of Granada, 18071 Granada, Spain; Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, 18016 Granada, Spain; Instituto de Investigación Biosanitaria de Granada ibs.GRANADA, 18012 Granada, Spain; Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain; Excellence Research Unit Modelling Nature (MNat), University of Granada, 18016 Granada, Spain; BioFab i3D - Biofabrication and 3D (bio)printing laboratory, University of Granada, 18100 Granada, Spain
| | - Aixa Aguilera-Garrido
- Department of Applied Physics, Faculty of Science, University of Granada, 18071 Granada, Spain
| | - Juan Antonio Marchal
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, 18016 Granada, Spain; Instituto de Investigación Biosanitaria de Granada ibs.GRANADA, 18012 Granada, Spain; Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain; Excellence Research Unit Modelling Nature (MNat), University of Granada, 18016 Granada, Spain; BioFab i3D - Biofabrication and 3D (bio)printing laboratory, University of Granada, 18100 Granada, Spain
| | - Saúl A Navarro-Marchal
- Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, 18016 Granada, Spain; Excellence Research Unit Modelling Nature (MNat), University of Granada, 18016 Granada, Spain; Cancer Research UK Edinburgh Centre, Institute of Genetics and Cancer, University of Edinburgh, EH4 2XU Edinburgh, UK.
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PEGylated and functionalized polylactide-based nanocapsules: An overview. Int J Pharm 2023; 636:122760. [PMID: 36858134 DOI: 10.1016/j.ijpharm.2023.122760] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2022] [Revised: 02/08/2023] [Accepted: 02/17/2023] [Indexed: 03/03/2023]
Abstract
Polymeric nanocapsules (NC) are versatile mixed vesicular nanocarriers, generally containing a lipid core with a polymeric wall. They have been first developed over four decades ago with outstanding applicability in the cosmetic and pharmaceutical fields. Biodegradable polyesters are frequently used in nanocapsule preparation and among them, polylactic acid (PLA) derivatives and copolymers, such as PLGA and amphiphilic block copolymers, are widely used and considered safe for different administration routes. PLA functionalization strategies have been developed to obtain more versatile polymers and to allow the conjugation with bioactive ligands for cell-targeted NC. This review intends to provide steps in the evolution of NC since its first report and the recent literature on PLA-based NC applications. PLA-based polymer synthesis and surface modifications are included, as well as the use of NC as a novel tool for combined treatment, diagnostics, and imaging in one delivery system. Furthermore, the use of NC to carry therapeutic and/or imaging agents for different diseases, mainly cancer, inflammation, and infections is presented and reviewed. Constraints that impair translation to the clinic are discussed to provide safe and reproducible PLA-based nanocapsules on the market. We reviewed the entire period in the literature where the term "nanocapsules" appears for the first time until the present day, selecting original scientific publications and the most relevant patent literature related to PLA-based NC. We presented to readers a historical overview of these Sui generis nanostructures.
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12
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Cai L, Gan M, Regenstein JM, Luan Q. Improving the biological activities of astaxanthin using targeted delivery systems. Crit Rev Food Sci Nutr 2023; 64:6902-6923. [PMID: 36779336 DOI: 10.1080/10408398.2023.2176816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/14/2023]
Abstract
The antioxidant and anti-inflammatory properties of astaxanthin (AST) enable it to protect against oxidative stress-related and inflammatory diseases with a range of biological effects. These activities provide the potential to develop healthier food products. Therefore, it would be beneficial to design delivery systems for AST to overcome its low stability, control its release, and/or improve its bioavailability. This review discusses the basis for AST's various biological activities and the factors limiting these activities, including stability, solubility, and bioavailability. It also discusses the different systems available for the targeted delivery of AST and their applications in enhancing the biological activity of AST. These include systems that are candidates for preventive and therapeutic effects, which include nerves, liver, and skin, particularly for possible cancer reduction. Targeted delivery of AST to specific regions of the gastrointestinal tract, or more selectively to target tissues and cells, can be achieved using targeted delivery systems to increase the biological activities of AST.
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Affiliation(s)
- Luyun Cai
- Ningbo Innovation Center, College of Biosystems Engineering and Food Science, Zhejiang University, Ningbo, Zhejiang, China
| | - Miaoyu Gan
- Ningbo Innovation Center, College of Biosystems Engineering and Food Science, Zhejiang University, Ningbo, Zhejiang, China
| | - Joe M Regenstein
- Department of Food Science, Cornell University, Ithaca, New York, USA
| | - Qian Luan
- Ningbo Innovation Center, College of Biosystems Engineering and Food Science, Zhejiang University, Ningbo, Zhejiang, China
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Mehandole A, Walke N, Mahajan S, Aalhate M, Maji I, Gupta U, Mehra NK, Singh PK. Core-Shell Type Lipidic and Polymeric Nanocapsules: the Transformative Multifaceted Delivery Systems. AAPS PharmSciTech 2023; 24:50. [PMID: 36703085 DOI: 10.1208/s12249-023-02504-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 01/03/2023] [Indexed: 01/28/2023] Open
Abstract
Amongst the several nano-drug delivery systems, lipid or polymer-based core-shell nanocapsules (NCs) have garnered much attention of researchers owing to its multidisciplinary properties and wide application. NCs are structured core-shell systems in which the core is an aqueous or oily phase protecting the encapsulated drug from environmental conditions, whereas the shell can be lipidic or polymeric. The core is stabilized by surfactant/lipids/polymers, which control the release of the drug. The presence of a plethora of biocompatible lipids and polymers with the provision of amicable surface modifications makes NCs an ideal choice for precise drug delivery. In the present article, multiple lipidic and polymeric NC (LNCs and PNCs) systems are described with an emphasis on fabrication methods and characterization techniques. Far-reaching applications as a carrier or delivery system are demonstrated for oral, parenteral, nasal, and transdermal routes of administration to enhance the bioavailability of hard-to-formulate drugs and to achieve sustained and targeted delivery. This review provide in depth understanding on core-shell NC's mechanism of absorption, surface modification, size tuning, and toxicity moderation which overshadows the drawbacks of conventional approaches. Additionally, the review shines a spotlight on the current challenges associated with core-shell NCs and applications in the foreseeable future.
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Affiliation(s)
- Arti Mehandole
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, Telangana, India
| | - Nikita Walke
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, Telangana, India
| | - Srushti Mahajan
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, Telangana, India
| | - Mayur Aalhate
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, Telangana, India
| | - Indrani Maji
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, Telangana, India
| | - Ujala Gupta
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, Telangana, India
| | - Neelesh Kumar Mehra
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, Telangana, India
| | - Pankaj Kumar Singh
- Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad, 500037, Telangana, India.
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14
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Mohammad AA, Amer HM, El-Sawy SM, Youssef DA, Nour SA, Soliman GM. Nematicidal activity of sweet annie and garden cress nano-formulations and their impact on the vegetative growth and fruit quality of tomato plants. Sci Rep 2022; 12:22302. [PMID: 36566273 PMCID: PMC9789970 DOI: 10.1038/s41598-022-26819-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2022] [Accepted: 12/20/2022] [Indexed: 12/25/2022] Open
Abstract
Root-knot nematode is one of the major problems that face the agricultural production of several vegetable crops. Chemical nematicides have been banned because of their healthy and environmental undesirable attributes. So, this study aimed to evaluate the potential use of sweet annie (Artimisia annua) and garden cress (Lepidium sativum) as green routes for the development of effective and eco-friendly alternative nematicides. Nematicidal activity of sweet annie and garden cress aqueous extracts (500 g/L) in the original and nano-forms were evaluated against Meloidogyne incognita in tomato planted in infected soil under greenhouse conditions. Nineteen phenolic compounds were identified in A. annua extract, which was dominated by chlorogenic acid (5059 µg/100 mL), while 11 compounds were identified in L. sativum extract, that dominated by p-hydroxybenzoic acid (3206 μg/100 mL). Nano-particles were characterized with smooth surface, spherical shape and small size (50-100 nm). Under laboratory, the nano-formulations showed mortality percentage of M. incognita J2 greater than the original extract from. Vegetative growth parameters of tomato plants treated with A. annua and L. sativum extracts significantly improved compared to the control plants. Also, biochemical analysis revealed that the extracts were able to induce tomato plants towards the accumulation of phenolic compounds and increasing the activity of defensive enzymes (protease, polyphenol oxidase and chitinase) resulting in systemic resistance. Regarding tomato fruits yield and quality, the studied treatments significantly improved the yield and physicochemical parameters of tomato fruits in terms of fruit weight, diameter, TSS, pH, lycopene content and color attributes gaining higher sensorial acceptance by the panelist. Generally, both extracts represent promising nematicide alternatives and have potential use in crop management. The nano-form of A. annua extract outperformed the nematicidal activity of other studied treatments.
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Affiliation(s)
- Ayman A Mohammad
- Food Technology Department, National Research Centre, Dokki, 12622, Cairo, Egypt.
| | - Heba M Amer
- Medicinal and Aromatic Plants Research Department, National Research Centre, Dokki, 12622, Cairo, Egypt.
| | - Sameh M El-Sawy
- Vegetable Research Department, National Research Centre, Dokki, 12622, Cairo, Egypt
| | - Dalia A Youssef
- Pests and Plant Protection Department, National Research Centre, Dokki, 12622, Cairo, Egypt
| | - Shaimaa A Nour
- Chemistry of Natural and Microbial Products Department, National Research Centre, Dokki, 12622, Cairo, Egypt
| | - Gaziea M Soliman
- Plant Pathology Department, Nematology Unit, National Research Centre, Dokki, 12622, Cairo, Egypt
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15
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Wang Z, Sun C, Wang R. Macrocycle-Surfaced Polymer Nanocapsules: An Emerging Paradigm for Biomedical Applications. Bioconjug Chem 2022; 33:2254-2261. [PMID: 35436111 DOI: 10.1021/acs.bioconjchem.2c00102] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
In the recent decade, macrocycle-surfaced polymer nanocapsules have been developed and studied as potential drug carriers. In particular, a unique group of these nanocapsules were constructed from a covalently self-assembled polymer network based on several classic macrocycles including cucurbituril, pillararene, and calixarene. The unique structure of these nanocapsules consists of a liquid or solid core and a shell laced with macrocycles in which the macrocycles not only act as the shell matrix of the nanocapsules but also allow further facile, modular functionalization via host-guest interactions with guest-tagged molecules. More interestingly, when a responsive cross-linker was introduced between the macrocycles, the payload inside the nanocapsules could be selectively released in the presence of typical hallmarks of certain diseases, which is of great interest for biomedical applications. In this Topical Review, macrocycle-surfaced polymer nanocapsules derived from covalently self-assembled polymer networks are introduced systemically with a focus on the molecular design and biomedical applications.
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Affiliation(s)
- Ziyi Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China
| | - Chen Sun
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China
| | - Ruibing Wang
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR 999078, China.,Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macau SAR 999078, China
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16
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Arvind Ahire S, Ashok Bachhav A, Bhavsing Pawar T, Sonu Jagdale B, Vitthal Patil A, Bhimrao Koli P. The augmentation of nanotechnology era: A concise review on fundamental concepts of nanotechnology and applications in material science and technology. RESULTS IN CHEMISTRY 2022. [DOI: 10.1016/j.rechem.2022.100633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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17
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Pinelli F, Saadati M, Rossetti A, Rossi F, Sacchetti A. On the influence of polyethyleneimine modification in nanogel-driven drug delivery. Colloids Surf A Physicochem Eng Asp 2022. [DOI: 10.1016/j.colsurfa.2022.130623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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18
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Choi KA, Kim JH, Ryu K, Kaushik N. Current Nanomedicine for Targeted Vascular Disease Treatment: Trends and Perspectives. Int J Mol Sci 2022; 23:12397. [PMID: 36293254 PMCID: PMC9604340 DOI: 10.3390/ijms232012397] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Revised: 10/04/2022] [Accepted: 10/14/2022] [Indexed: 12/19/2022] Open
Abstract
Nanotechnology has been developed to deliver cargos effectively to the vascular system. Nanomedicine is a novel and effective approach for targeted vascular disease treatment including atherosclerosis, coronary artery disease, strokes, peripheral arterial disease, and cancer. It has been well known for some time that vascular disease patients have a higher cancer risk than the general population. During atherogenesis, the endothelial cells are activated to increase the expression of adhesion molecules such as Intercellular Adhesion Molecule 1 (ICAM-1), Vascular cell adhesion protein 1 (VCAM-1), E-selectin, and P-selectin. This biological activation of endothelial cells gives a targetability clue for nanoparticle strategies. Nanoparticle formation has a passive targeting pathway due to the increased adhesion molecule expression on the cell surface as well as increased cell activation. In addition, the VCAM-1-targeting peptide has been widely used to target the inflamed endothelial cells. Biomimetic nanoparticles using platelet and leukocyte membrane fragment strategies have been promising techniques for targeted vascular disease treatment. Cyclodextrin, a natural oligosaccharide with a hydrophobic cavity, increase the solubility of cholesterol crystals at the atherosclerotic plaque site and has been used to deliver the hydrophobic drug statin as a therapeutic in a targeted manner. In summary, nanoparticles decorated with various targeting molecules will be an effective and promising strategy for targeted vascular disease treatment.
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Affiliation(s)
- Kyung-A Choi
- National Institute of Medical Welfare, Kangnam University, Yongin 16979, Korea
| | - June Hyun Kim
- Department of Biotechnology, The University of Suwon, Suwon 18323, Korea
| | - Kitae Ryu
- Department of Biotechnology, The University of Suwon, Suwon 18323, Korea
| | - Neha Kaushik
- Department of Biotechnology, The University of Suwon, Suwon 18323, Korea
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El Gohary NA, Mahmoud A, Ashraf Nazmy M, Zaabalawi R, El Zahar L, Khalil ISM, Mitwally ME. Magnetic polycaprolactone microspheres: drug encapsulation and control. INT J POLYM MATER PO 2022. [DOI: 10.1080/00914037.2022.2132248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Affiliation(s)
- Nesrine Abdelrehim El Gohary
- Pharmaceutical Chemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Abdelrahman Mahmoud
- Materials Engineering Department, Faculty of Engineering and Materials Science, German University in Cairo, Cairo, Egypt
| | | | - Rami Zaabalawi
- Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Loaa El Zahar
- Faculty of Media Engineering and Technology, German University in Cairo, Cairo, Egypt
| | - Islam S. M. Khalil
- Department of Biomechanical Engineering, University of Twente, Enschede, the Netherlands
| | - Mohamed E. Mitwally
- Materials Engineering Department, Faculty of Engineering and Materials Science, German University in Cairo, Cairo, Egypt
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20
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Iqbal N, Braxton TM, Anastasiou A, Raif EM, Chung CKY, Kumar S, Giannoudis PV, Jha A. Dicalcium Phosphate Dihydrate Mineral Loaded Freeze-Dried Scaffolds for Potential Synthetic Bone Applications. MATERIALS (BASEL, SWITZERLAND) 2022; 15:6245. [PMID: 36143561 PMCID: PMC9506122 DOI: 10.3390/ma15186245] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 08/19/2022] [Accepted: 08/30/2022] [Indexed: 06/16/2023]
Abstract
Dicalcium Phosphate Dihydrate (DCPD) mineral scaffolds alone do not possess the mechanical flexibility, ease of physicochemical properties' tuneability or suitable porosity required for regenerative bone scaffolds. Herein, we fabricated highly porous freeze-dried chitosan scaffolds embedded with different concentrations of Dicalcium Phosphate Dihydrate (DCPD) minerals, i.e., 0, 20, 30, 40 and 50 (wt)%. Increasing DCPD mineral concentration led to increased scaffold crystallinity, where the % crystallinity for CH, 20, 30, 40, and 50-DCPD scaffolds was determined to be 0.1, 20.6, 29.4, 38.8 and 69.9%, respectively. Reduction in scaffold pore size distributions was observed with increasing DCPD concentrations of 0 to 40 (wt)%; coalescence and close-ended pore formation were observed for 50-DCPD scaffolds. 50-DCPD scaffolds presented five times greater mechanical strength than the DCPD mineral-free scaffolds (CH). DCPD mineral enhanced cell proliferation for the 20, 30 and 40-DCPD scaffolds. 50-DCPD scaffolds presented reduced pore interconnectivity due to the coalescence of many pores in addition to the creation of closed-ended pores, which were found to hinder osteoblast cell proliferation.
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Affiliation(s)
- Neelam Iqbal
- School of Chemical and Process Engineering, University of Leeds, Leeds LS2 9JT, UK
| | | | - Antonios Anastasiou
- Department of Chemical Engineering and Analytical Science, University of Manchester, Manchester M1 3AL, UK
| | - El Mostafa Raif
- Faculty of Medicine and Health, School of Dentistry, University of Leeds, Leeds LS2 9JT, UK
| | | | - Sandeep Kumar
- Faculty of Medicine and Health, School of Dentistry, University of Leeds, Leeds LS2 9JT, UK
| | - Peter V. Giannoudis
- Academic Department of Trauma and Orthopaedic Surgery, School of Medicine, University of Leeds, Leeds LS2 9JT, UK
| | - Animesh Jha
- School of Chemical and Process Engineering, University of Leeds, Leeds LS2 9JT, UK
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21
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Li X, Zhang S, Chen Y, Wang S, Xu Q, Xu J. Designing anisotropic inorganic nanocapsules via self-assembly of polymer-like ultrathin Au nanowires. NANOSCALE 2022; 14:10060-10066. [PMID: 35791869 DOI: 10.1039/d2nr01749k] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Anisotropic assembly of nanomaterials into hollow structures is an attractive technique in biomedicine and biosensing. Commonly used polymer materials are easy to assemble yet it is hard to form anisotropic morphologies. Here in this work, we successfully prepared a novel gold nanocapsule with an anisotropic ellipsoidal shape and cavity structure by the self-assembly of ultrathin Au nanowires. The assembly mechanism is further studied by tuning the assembly conditions such as nanowire concentration, solvent composition, and temperature. It is found that the controlling forces of the nanowire assembly process are mainly the symmetric interfacial tension and the asymmetric nanowire deformation potential, which contribute together to result in anisotropic nanocapsules. Finally, the obtained Au nanocapsules were used as nanocarriers to load pyrene as a model drug, showing great drug loading ability and pH-responsive drug release behavior. We believe that this unique anisotropic assembly product will bring new insights into nanostructure design and soft matter research.
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Affiliation(s)
- Xingyun Li
- Department of Physics, Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Laboratory for Soft Functional Materials, Xiamen University, Xiamen 361005, Fujian, China.
| | - Sai Zhang
- Department of Physics, Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Laboratory for Soft Functional Materials, Xiamen University, Xiamen 361005, Fujian, China.
| | - Yuan Chen
- Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore 119077
| | - Shanshan Wang
- Department of Chemistry, College of Materials, Xiamen University, Xiamen 361005, Fujian, China
| | - Qingchi Xu
- Department of Physics, Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Laboratory for Soft Functional Materials, Xiamen University, Xiamen 361005, Fujian, China.
| | - Jun Xu
- Department of Physics, Research Institute for Biomimetics and Soft Matter, Fujian Provincial Key Laboratory for Soft Functional Materials, Xiamen University, Xiamen 361005, Fujian, China.
- Shenzhen Research Institute of Xiamen University, Shenzhen 518057, Guangdong, China
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22
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Intranasally administered melatonin core-shell polymeric nanocapsules: A promising treatment modality for cerebral ischemia. Life Sci 2022; 306:120797. [PMID: 35841976 DOI: 10.1016/j.lfs.2022.120797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 06/30/2022] [Accepted: 07/08/2022] [Indexed: 11/22/2022]
Abstract
AIMS The neurohormone melatonin (MEL) has been reported as a promising neuroprotective molecule, however it suffers pharmaceutical limitations such as poor solubility and low bioavailability, which hinder its pharmacological and clinical potential. In the current work, MEL was loaded in core-shell nanocarrier system; polymeric nanocapsules (PNCs), and assessed for its potential in cerebral ischemia reperfusion injury rat model when administered intranasally. KEY FINDINGS Adopting a D-optimal factorial design, MEL-PNCs were successfully formulated using the nanoprecipitation technique. MEL-PNCs exhibited a particle size ranging from 143.5 to 444 nm, negative zeta potential values ranging from -24.2 to -38.7 mV, cumulative release % for MEL ranging from 36.79 to 41.31 % over 8 h period, with overall good storage properties. The selected MEL-PNCs formulation displayed 8-fold higher permeation than the drug solution across sheep nasal mucosa. MEL-PNCs administered intranasally decreased oxidative stress and hippocampal inflammation, and the histological examination revealed the significant restoration of hippocampal neurons. SIGNIFICANCE MEL-PNCs administered intranasally could be a promising treatment modality in brain ischemia.
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23
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Frank LA, Gazzi RP, Pohlmann AR, Guterres SS, Contri RV. Evaluation of an efficient and skin-adherent semisolid sunscreen nanoformulation. Skin Pharmacol Physiol 2022; 35:291-298. [PMID: 35705070 DOI: 10.1159/000525176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Accepted: 04/14/2022] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Sunscreens are substances applied on the skin surface to protect the skin from the harmful effects of UV light. Nanoparticles can increase the retention time of the sunscreen on the skin surface and its efficacy, by acting as physical barriers. The present investigation aimed to prepare and characterize benzophenone-3-loaded lipid core nanocapsules coated with chitosan (CH-LNC) and, after obtaining a suitable semisolid formulation for skin application, to evaluate the influence of the nanocapsules chitosan-coating on the skin adhesion and photoprotective effect of the sunscreen. METHODS CH-LNC were obtained by the interfacial deposition of pre-formed polymer. The semisolid formulation was obtained using hydroxyethyl cellulose as gel-forming polymer. Skin adhesion experiments were performed by keeping skin membranes with formulation under water at 32oC for up to 60 minutes. Photoprotective effect was analyzed by the capacity of the formulations to protect a photo unstable substance (resveratrol) from degradation under UV light. RESULTS CH-LNC presented size of around 150nm, with low polydispersity, positive zeta potential, due to chitosan, and benzophenone-3 encapsulation efficiency of close to 100% (3mg/mL). The proposed gel presented suitable consistence and pH for skin application. Although coated and uncoated LNC increased benzonphenone-3 skin adhesion after 10 minutes of water immersion, only the nanoparticles coated with chitosan were able to do so after 60 minutes. CH-LNC increased the photoprotection of the sunscreen under UVA and UVB light after 60 minutes of exposure, probably due to the bioadhesion and film-forming properties of chitosan. CONCLUSION The chitosan coating of benzophenone-3-loaded LNC increased the skin adhesion and the photoprotective effect of the sunscreen.
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Affiliation(s)
- Luiza Abrahão Frank
- Faculdade de Farmácia Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
- Programa de Pós-Graduação em Ciências Farmacêuticas, PPGCF, Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
| | - Rafaela Pletsch Gazzi
- Faculdade de Farmácia Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
- Programa de Pós-Graduação em Ciências Farmacêuticas, PPGCF, Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
| | - Adriana Raffin Pohlmann
- Faculdade de Farmácia Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
- Programa de Pós-Graduação em Ciências Farmacêuticas, PPGCF, Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
- Programa de Pós-Graduação em Nanotecnologia Farmacêutica, PPGNANO, Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
| | - Silvia Stanisçuaski Guterres
- Faculdade de Farmácia Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
- Programa de Pós-Graduação em Ciências Farmacêuticas, PPGCF, Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
- Programa de Pós-Graduação em Nanotecnologia Farmacêutica, PPGNANO, Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
| | - Renata Vidor Contri
- Faculdade de Farmácia Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
- Programa de Pós-Graduação em Ciências Farmacêuticas, PPGCF, Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
- Programa de Pós-Graduação em Nanotecnologia Farmacêutica, PPGNANO, Universidade Federal do Rio grande do Sul, Porto Alegre, Brazil
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Dellali KZ, Dellali M, Raţă DM, Cadinoiu AN, Atanase LI, Popa M, Spataru MC, Solcan C. Assessment of Physicochemical and In Vivo Biological Properties of Polymeric Nanocapsules Based on Chitosan and Poly( N-vinyl pyrrolidone- alt-itaconic anhydride). Polymers (Basel) 2022; 14:polym14091811. [PMID: 35566980 PMCID: PMC9104533 DOI: 10.3390/polym14091811] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 04/13/2022] [Accepted: 04/19/2022] [Indexed: 02/07/2023] Open
Abstract
Drug delivery is an important field of nanomedicine, and its aim is to deliver specific active substances to a precise site of action in order to produce a desired pharmacological effect. In the present study nanocapsules were obtained by a process of interfacial condensation between chitosan (dissolved in the aqueous phase) and poly(N-vinyl pyrrolidone-alt-itaconic anhydride), a highly reactive copolymer capable of easily opening the anhydride ring under the action of amine groups of chitosan. The formed amide bonds led to the formation of a hydrogel membrane. The morphology of the obtained nanocapsules, their behavior in aqueous solution of physiological pH, and their ability to encapsulate and release a model drug can be modulated by the parameters of the synthesis process, such as the molar ratio between functional groups of polymers and the ratio of the phases in which the polymers are solubilized. Although a priori both polymers are biocompatible, this paper reports the results of a very detailed in vivo study conducted on experimental animals which have received the obtained nanocapsules by three administration routes—intraperitoneal, subcutaneous, and oral. The organs taken from the animals’ kidney, liver, spleen, and lung and analyzed histologically demonstrated the ability of nanocapsules to stimulate the monocytic macrophage system without producing inflammatory changes. Moreover, their in vivo behavior has been shown to depend not only on the route of administration but also on the interaction with the cells of the organs with which they come into contact. The results clearly argue the biocompatibility of nanocapsules and hence the possibility of their safe use in biomedical applications.
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Affiliation(s)
- Kheira Zanoune Dellali
- Faculty of Technology, University Hassiba Benbouali, BP 151, Chlef 02000, Algeria; (K.Z.D.); (M.D.)
| | - Mohammed Dellali
- Faculty of Technology, University Hassiba Benbouali, BP 151, Chlef 02000, Algeria; (K.Z.D.); (M.D.)
| | - Delia Mihaela Raţă
- Faculty of Medical Dentistry, Apollonia University of Iasi, Pacurari Street, No. 11, 700511 Iasi, Romania;
- Correspondence: (D.M.R.); (L.I.A.); (M.P.)
| | - Anca Niculina Cadinoiu
- Faculty of Medical Dentistry, Apollonia University of Iasi, Pacurari Street, No. 11, 700511 Iasi, Romania;
| | - Leonard Ionut Atanase
- Faculty of Medical Dentistry, Apollonia University of Iasi, Pacurari Street, No. 11, 700511 Iasi, Romania;
- Correspondence: (D.M.R.); (L.I.A.); (M.P.)
| | - Marcel Popa
- Faculty of Medical Dentistry, Apollonia University of Iasi, Pacurari Street, No. 11, 700511 Iasi, Romania;
- Academy of Romanian Scientists, Splaiul Independentei Street, No. 54, 050094 Bucharest, Romania
- Correspondence: (D.M.R.); (L.I.A.); (M.P.)
| | - Mihaela-Claudia Spataru
- Public Health Departament, Faculty of Veterinary Medicine, Ion Ionescu de la Brad University of Life Sciences, Mihail Sadoveanu Alley, No. 8, 700489 Iasi, Romania; (M.-C.S.); (C.S.)
| | - Carmen Solcan
- Public Health Departament, Faculty of Veterinary Medicine, Ion Ionescu de la Brad University of Life Sciences, Mihail Sadoveanu Alley, No. 8, 700489 Iasi, Romania; (M.-C.S.); (C.S.)
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25
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Kuskov A, Nikitovic D, Berdiaki A, Shtilman M, Tsatsakis A. Amphiphilic Poly- N-vinylpyrrolidone Nanoparticles as Carriers for Nonsteroidal, Anti-Inflammatory Drugs: Pharmacokinetic, Anti-Inflammatory, and Ulcerogenic Activity Study. Pharmaceutics 2022; 14:925. [PMID: 35631510 PMCID: PMC9147221 DOI: 10.3390/pharmaceutics14050925] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 04/21/2022] [Accepted: 04/22/2022] [Indexed: 02/01/2023] Open
Abstract
Nanoparticles are increasingly utilized as drug delivery agents. Previously, we have developed a drug delivery system based on amphiphilic derivatives of poly-N-vinylpyrrolidone (PVP-OD4000) with excellent biocompatibility. In the current study, we assessed the pharmacokinetics, anti-inflammatory profile, and ulcerogenic potential of indomethacin (IMC)-loaded PVP-OD4000 nanoparticles compared to the free drug. Wistar male rats were utilized for a pharmacokinetics study and an anti-inflammatory study. Loaded IMC exhibited a slower elimination rate (p < 0.05) and a higher blood plasma concentration at 8 and 24 h after intraperitoneal injection compared with free IMC. In addition, decreased uptake of loaded IMC in the liver and kidney compared to free IMC (p < 0.05) was detected. Furthermore, PVP-OD4000 nanoparticles loaded with IMC showed an enhanced anti-inflammatory effect compared to free IMC (p < 0.05) in carrageenan-induced and complete Freund’s adjuvant-induced−(CFA) sub-chronic and chronic paw edema treatment (p < 0.01; p < 0.01). Notably, upon oral administration of loaded IMC, animals had a significantly lower ulcer score and Paul’s Index (3.9) compared to the free drug (p < 0.05). The obtained results suggest that IMC loaded to PVP nanoparticles exhibit superior anti-inflammatory activity in vivo and a safe gastrointestinal profile and pose a therapeutic alternative for the currently available NSAIDs’ administration.
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Affiliation(s)
- Andrey Kuskov
- Department of Technology of Chemical Pharmaceutical and Cosmetic Substances, D. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia;
- Department of Biomaterials, D. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia;
| | - Dragana Nikitovic
- Laboratory of Histology-Embryology, Medical School, Voutes Campus, University of Crete, 71003 Heraklion, Greece;
| | - Aikaterini Berdiaki
- Laboratory of Histology-Embryology, Medical School, Voutes Campus, University of Crete, 71003 Heraklion, Greece;
| | - Mikhail Shtilman
- Department of Biomaterials, D. Mendeleev University of Chemical Technology of Russia, 125047 Moscow, Russia;
| | - Aristidis Tsatsakis
- Center of Toxicology Science & Research, Division of Morphology, Medical School, Voutes Campus, University of Crete, 71003 Heraklion, Greece;
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Xiao Z, Liu H, Zhao Q, Niu Y, Chen Z, Zhao D. Application of microencapsulation technology in silk fibers. J Appl Polym Sci 2022. [DOI: 10.1002/app.52351] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Zuobing Xiao
- School of Perfume and Aroma Technology Shanghai Institute of Technology Shanghai China
- School of Agriculture and Biology Shanghai Jiaotong University Shanghai China
| | - Huiqin Liu
- School of Perfume and Aroma Technology Shanghai Institute of Technology Shanghai China
| | - Qixuan Zhao
- School of Perfume and Aroma Technology Shanghai Institute of Technology Shanghai China
| | - Yunwei Niu
- School of Perfume and Aroma Technology Shanghai Institute of Technology Shanghai China
| | - Ziqian Chen
- School of Perfume and Aroma Technology Shanghai Institute of Technology Shanghai China
| | - Di Zhao
- School of Perfume and Aroma Technology Shanghai Institute of Technology Shanghai China
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de Lima LS, Mortari MR. Therapeutic nanoparticles in the brain: A review of types, physicochemical properties and challenges. Int J Pharm 2022; 612:121367. [PMID: 34896565 DOI: 10.1016/j.ijpharm.2021.121367] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 11/25/2021] [Accepted: 12/06/2021] [Indexed: 12/18/2022]
Abstract
One of the main obstacles in the treatment of neurological diseases, perhaps the biggest one, is the delivery of therapeutic compounds to the central nervous system, and nanoparticles are promising tools to overcome this challenge. Different types of nanoparticles may be used as delivery systems, including liposomes, carbon nanotubes, and dendrimers. Nevertheless, these nanoparticles must display characteristics to be useful in brain drug delivery, such as stability, permeability to blood vessels, biocompatibility, and specificity. All of these aspects are intrinsically related to the physicochemical properties of nanoformulations: size, composition, electric charge, hydrophobicity, mucoadherence, permeability to the blood-brain barrier, and many others. Furthermore, there are challenging hindrances involved in the development and application of nanoparticles - hence the importance of studying and understanding these pharmaceutical tools.
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Affiliation(s)
- Larissa Silva de Lima
- Laboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, Campus Universitário Darcy Ribeiro, University of Brasilia, 70910-900 Brasilia, Distrito Federal, Brazil
| | - Márcia Renata Mortari
- Laboratory of Neuropharmacology, Department of Physiological Sciences, Institute of Biological Sciences, Campus Universitário Darcy Ribeiro, University of Brasilia, 70910-900 Brasilia, Distrito Federal, Brazil.
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Ramos R, Bernard J, Ganachaud F, Miserez A. Protein‐Based Encapsulation Strategies: Toward Micro‐ and Nanoscale Carriers with Increased Functionality. SMALL SCIENCE 2022. [DOI: 10.1002/smsc.202100095] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Affiliation(s)
- Ricardo Ramos
- Université de Lyon INSA Lyon CNRS IMP 5223 Villeurbanne Cedex 69621 France
- INSA-Lyon, IMP Villeurbanne F-69621 France
- CNRS, UMR 5223 Ingénierie des Matériaux Polymères Villeurbanne F-69621 France
| | - Julien Bernard
- Université de Lyon INSA Lyon CNRS IMP 5223 Villeurbanne Cedex 69621 France
- INSA-Lyon, IMP Villeurbanne F-69621 France
- CNRS, UMR 5223 Ingénierie des Matériaux Polymères Villeurbanne F-69621 France
| | - François Ganachaud
- Université de Lyon INSA Lyon CNRS IMP 5223 Villeurbanne Cedex 69621 France
- INSA-Lyon, IMP Villeurbanne F-69621 France
- CNRS, UMR 5223 Ingénierie des Matériaux Polymères Villeurbanne F-69621 France
| | - Ali Miserez
- Biological and Biomimetic Material Laboratory Center for Sustainable Materials (SusMat), School of Materials Science and Engineering Nanyang Technological University (NTU) 50 Nanyang Avenue Singapore 637 553 Singapore
- School of Biological Sciences NTU 59 Nanyang Drive Singapore 636921 Singapore
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Zancan LR, Bruinsmann FA, Paese K, Türck P, Bahr A, Zimmer A, Carraro CC, Schenkel PC, Belló-Klein A, Schwertz CI, Driemeier D, Pohlmann AR, Guterres SS. Oral delivery of ambrisentan-loaded lipid-core nanocapsules as a novel approach for the treatment of pulmonary arterial hypertension. Int J Pharm 2021; 610:121181. [PMID: 34653563 DOI: 10.1016/j.ijpharm.2021.121181] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 10/04/2021] [Accepted: 10/08/2021] [Indexed: 12/29/2022]
Abstract
Ambrisentan (AMB) is an orphan drug approved for oral administration that has been developed for the treatment of pulmonary arterial hypertension (PAH), a chronic and progressive pathophysiological state that might result in death if left untreated. Lipid-core nanocapsules (LNCs) are versatile nanoformulations capable of loading lipophilic drugs for topical, vaginal, oral, intravenous, pulmonary, and nasal administration. Our hypothesis was to load AMB into these nanocapsules (LNCamb) and test their effect on slowing or reducing the progression of monocrotaline-induced PAH in a rat model, upon oral administration. LNCamb displayed a unimodal distribution of diameters (around 200 nm), negative zeta potential (-11.5 mV), high encapsulation efficiency (78%), spherical shape, and sustained drug release (50-60% in 24 h). The in vivo pharmacodynamic effect of the LNCamb group was evaluated by observing the echocardiography, hemodynamic, morphometric, and histological data, which showed a significant decrease in PAH in this group, as compared to the control group (AMBsolution). LNCamb showed the benefit of reversing systolic dysfunction and preventing vascular remodeling with greater efficacy than that observed in the control group. The originality and contribution of our work reveal the promising value of this nanoformulation as a novel therapeutic strategy for PAH treatment.
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Affiliation(s)
- Lali Ronsoni Zancan
- Programa de Pós-Graduação em Nanotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil
| | - Franciele Aline Bruinsmann
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil
| | - Karine Paese
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil
| | - Patrick Türck
- Laboratório de Fisiologia Cardiovascular e Espécies Ativas de Oxigênio, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite 500, Porto Alegre 90050-170, RS, Brazil
| | - Alan Bahr
- Laboratório de Fisiologia Cardiovascular e Espécies Ativas de Oxigênio, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite 500, Porto Alegre 90050-170, RS, Brazil
| | - Alexsandra Zimmer
- Laboratório de Fisiologia Cardiovascular e Espécies Ativas de Oxigênio, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite 500, Porto Alegre 90050-170, RS, Brazil
| | - Cristina Campos Carraro
- Laboratório de Fisiologia Cardiovascular e Espécies Ativas de Oxigênio, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite 500, Porto Alegre 90050-170, RS, Brazil
| | - Paulo Cavalheiro Schenkel
- Laboratório de Fisiologia Cardiovascular e Espécies Ativas de Oxigênio, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite 500, Porto Alegre 90050-170, RS, Brazil
| | - Adriane Belló-Klein
- Laboratório de Fisiologia Cardiovascular e Espécies Ativas de Oxigênio, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite 500, Porto Alegre 90050-170, RS, Brazil
| | - Claiton I Schwertz
- Setor de Patologia Veterinária, Departamento de Patologia Clínica Veterinária, Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves 9090, Porto Alegre 91540-000, RS, Brazil
| | - David Driemeier
- Setor de Patologia Veterinária, Departamento de Patologia Clínica Veterinária, Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves 9090, Porto Alegre 91540-000, RS, Brazil
| | - Adriana Raffin Pohlmann
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil
| | - Sílvia Stanisçuaski Guterres
- Programa de Pós-Graduação em Nanotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Ipiranga, 2752, Porto Alegre 90610-000, RS, Brazil.
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Isola LA, Chen TC, Elveny M, Alkaim AF, Thangavelu L, Kianfar E. Application of micro and porous materials as nano-reactors. REV INORG CHEM 2021. [DOI: 10.1515/revic-2021-0007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Abstract
In general, nanostructured materials with specific size, shape and geometry have unique and different properties from bulk materials. Using reaction media with nanometer and micrometer dimensions, they can produce new nanomaterials with interesting and remarkable properties. In general, nano-reactors are nanometer-sized chambers in which chemical reactions can take place. of course, nanoreactors are somehow part of the reaction, and this is the main difference between them and micro-reactors. One of the useful solutions to achieve the environment of nanoreactors is the use of porous materials, so due to the importance of nanoreactors, porous structures of silicate and zeolite are among the most prominent and widely used compounds in this group.
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Affiliation(s)
- Lawal Adedoyin Isola
- Department of Accounting and Finance , Landmark University , Omu-Aran , Nigeria
- Sustainable Development Goal 17 (Partnership for the Goals) Research Cluster, Landmark University , Omu-Aran , Nigeria
- SDG1 (Zero Hunger) Research Cluster, Landmark University , Omu-Aran , Nigeria
- SDG6 (Clean Energy) Research Cluster, Landmark University , Omu-Aran , Nigeria
| | | | - Marischa Elveny
- Data Science & Computational Intelligence Research Group , Universitas Sumatera Utara , Medan , Indonesia
| | - Ayad F. Alkaim
- Chemistry Department , College of Science for Women, University of Babylon , Hillah , Iraq
| | - Lakshmi Thangavelu
- Department of Pharmacology , Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University , Chennai , India
| | - Ehsan Kianfar
- SDG 8 (Decent Work and Economic Growth) Research Cluster, Landmark University , Omu-Aran , Nigeria
- Department of Chemical Engineering , Arak Branch, Islamic Azad University , Arak , Iran
- Young Researchers and Elite Club , Gachsaran Branch, Islamic Azad University , Gachsaran , Iran
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Lyophilization of Nanocapsules: Instability Sources, Formulation and Process Parameters. Pharmaceutics 2021; 13:pharmaceutics13081112. [PMID: 34452072 PMCID: PMC8400524 DOI: 10.3390/pharmaceutics13081112] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 07/09/2021] [Accepted: 07/15/2021] [Indexed: 01/20/2023] Open
Abstract
Polymeric nanocapsules have gained more and more interest in the medical sciences. Their core-shell structure offers numerous advantages, especially regarding their use as drug delivery systems. This review begins by presenting the different intrinsic sources of the instability of nanocapsules. The physical and chemical potential instabilities of nanocapsules reduce their shelf-life and constitute a barrier to their clinical use and to their commercialization. To overcome these issues, lyophilization is often used as a process of choice in the pharmaceutical industry especially when labile compounds are used. The state of the art of lyophilization nanocapsules is reviewed. The formulation properties and the process parameters are discussed for a complete understanding of their impact on the stability and storage of the final dried product. To assess the quality of the dried product, various characterization methods are also discussed.
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Nanoreactors: properties, applications and characterization. INTERNATIONAL JOURNAL OF CHEMICAL REACTOR ENGINEERING 2021. [DOI: 10.1515/ijcre-2021-0069] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Abstract
Nanoreactors are a type of chemical reactor that is used mostly in nanotechnology and nanobiotechnology. These unique reactors are critical to the operation of a nano foundry, which is essentially a foundry that produces goods on a nanoscale. Active sites, such as transitional metal species, can also be added to nanoreactors. In this situation, the NR’s limited area might impact reaction rate and mechanism by increasing the contacts between reactants and active sites and changing the concentration of the reactant at the active site. Immobilization of chiral active centers inside porous materials has received a lot of interest in this context, and there have been a lot of publications proving the benefits of nano space confinement in chemical processes. The specific mechanism in which enantioselectivities are strengthened has been clarified using molecular dynamics simulations. Nanoreactors are nanometer-sized chambers with the potential to improve chemical conversions by shielding catalysts from external effects and encapsulating reactors and catalysts in a tiny space for an extended period of time. Natural and synthetic nanoreactors are the two types of nanoreactors that can be found in general. The first group has a more selective function while also having a more complicated structure, whereas the second group has more variation and a simpler structure. Synthetic nanoreactors have so far been made with a variety of molecules and large types of molecules. The space inside the nanoreactors is a good environment for the production of various nanostructures, in addition to a wide range of chemical reactions. When chemical reactions are carried out in confined spaces with nanometer dimensions and micrometer volumes, the kinetics and the entire process path are altered. Nanoreactors are restricted areas used to execute specialized chemical processes. In the cells of living organisms, numerous simultaneous reactions are based on the same concept. As a result, various biological and chemical structures with nanoreactor characteristics are used in this strategy.
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AbdElhamid AS, Zayed DG, Heikal L, Khattab SN, Mady OY, El-Gizawy SA, Elzoghby AO. Recent advances in polymer shell oily-core nanocapsules for drug-delivery applications. Nanomedicine (Lond) 2021; 16:1613-1625. [PMID: 34189946 DOI: 10.2217/nnm-2021-0037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Polymeric nanocapsules are vesicular drug-delivery systems composed of an inner oily reservoir surrounded by polymeric membranes. Nanocapsules have various advantages over other nanovesicular systems such as providing controlled drug release properties. We discuss the recent advances in polymeric shell oily-core nanocapsules, illustrating the different types of polymers used and their implementation. Nanocapsules can be utilized for many purposes, especially encapsulation of highly lipophilic drugs. They have been shown to have variable applications, especially in cancer therapy, due to the ability of the polymeric shell to direct the loaded drugs to their target sites, as well as their high internalization efficacy. Those productive applications guaranteed their high potential as drug-delivery systems. However, their clinical development is still in an early stage.
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Affiliation(s)
- Ahmed S AbdElhamid
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Dina G Zayed
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Lamia Heikal
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - Sherine N Khattab
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, 21321, Egypt
| | - Omar Y Mady
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Sanaa A El-Gizawy
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Ahmed O Elzoghby
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
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34
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Recent Advances in Nanomaterials for Dermal and Transdermal Applications. COLLOIDS AND INTERFACES 2021. [DOI: 10.3390/colloids5010018] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The stratum corneum, the most superficial layer of the skin, protects the body against environmental hazards and presents a highly selective barrier for the passage of drugs and cosmetic products deeper into the skin and across the skin. Nanomaterials can effectively increase the permeation of active molecules across the stratum corneum and enable their penetration into deeper skin layers, often by interacting with the skin and creating the distinct sites with elevated local concentration, acting as reservoirs. The flux of the molecules from these reservoirs can be either limited to the underlying skin layers (for topical drug and cosmeceutical delivery) or extended across all the sublayers of the epidermis to the blood vessels of the dermis (for transdermal delivery). The type of the nanocarrier and the physicochemical nature of the active substance are among the factors that determine the final skin permeation pattern and the stability of the penetrant in the cutaneous environment. The most widely employed types of nanomaterials for dermal and transdermal applications include solid lipid nanoparticles, nanovesicular carriers, microemulsions, nanoemulsions, and polymeric nanoparticles. The recent advances in the area of nanomaterial-assisted dermal and transdermal delivery are highlighted in this review.
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Tedesco AC, Silva EPO, Jayme CC, Piva HL, Franchi LP. Cholesterol-rich nanoemulsion (LDE) as a novel drug delivery system to diagnose, delineate, and treat human glioblastoma. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 123:111984. [PMID: 33812612 DOI: 10.1016/j.msec.2021.111984] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 02/15/2021] [Accepted: 02/17/2021] [Indexed: 11/26/2022]
Abstract
We have prepared and characterized a cholesterol-rich nanoemulsion called LDE, a mimic of classic lipoprotein macromolecules, that can be applied as a new drug delivery system for aluminum phthalocyanine chloride (PcAlCl). The LDE containing PcAlCl system prepared herein had mean size and zeta potential of 127 nm and -29 mV, respectively, and encapsulation rate efficiency was 81%, and stability of 17 months. Compared to classical liposomes, LDE was more efficient, especially in brain diseases like glioblastoma (GBM), as revealed by tests on the U-87 MG cell line. The LDEPc formulation did not display dark cytotoxicity, as expected. The best light dose for LDEPc was 1.0 J·cm-2: its activity was 55% higher than PcAlCl in a compatible organic medium. In the U-87 MG cells, apoptosis was the preferential pathway activated by PDT. These results strongly support the use of LDE as a new theranostic system.
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Affiliation(s)
- Antonio Claudio Tedesco
- Department of Chemistry, Center of Nanotechnology and Tissue Engineering, Photobiology and Photomedicine Research Group, Faculty of Philosophy, Science and Letters of Ribeirão Preto, University of São Paulo (USP), 14040-901 Ribeirão Preto, SP, Brazil.
| | - Emanoel P O Silva
- Department of Chemistry, Center of Nanotechnology and Tissue Engineering, Photobiology and Photomedicine Research Group, Faculty of Philosophy, Science and Letters of Ribeirão Preto, University of São Paulo (USP), 14040-901 Ribeirão Preto, SP, Brazil
| | - Cristiano C Jayme
- Department of Chemistry, Center of Nanotechnology and Tissue Engineering, Photobiology and Photomedicine Research Group, Faculty of Philosophy, Science and Letters of Ribeirão Preto, University of São Paulo (USP), 14040-901 Ribeirão Preto, SP, Brazil
| | - Henrique L Piva
- Department of Chemistry, Center of Nanotechnology and Tissue Engineering, Photobiology and Photomedicine Research Group, Faculty of Philosophy, Science and Letters of Ribeirão Preto, University of São Paulo (USP), 14040-901 Ribeirão Preto, SP, Brazil
| | - Leonardo P Franchi
- Department of Chemistry, Center of Nanotechnology and Tissue Engineering, Photobiology and Photomedicine Research Group, Faculty of Philosophy, Science and Letters of Ribeirão Preto, University of São Paulo (USP), 14040-901 Ribeirão Preto, SP, Brazil; Departamento de Bioquímica e Biologia Molecular, Instituto de Ciências Biológicas (ICB) 2, Campus Samambaia, Universidade Federal de Goiás (UFG), 74690-900 Goiânia, GO, Brazil
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Theoretical analysis of the structural and electronic properties of the interaction of boron nitride diamantane nanocrystal with the drug hydroxyurea as an anticancer drug. J Mol Model 2021; 27:90. [PMID: 33611723 DOI: 10.1007/s00894-021-04711-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2020] [Accepted: 02/10/2021] [Indexed: 10/22/2022]
Abstract
The density functional theory calculations with hybrid B3LYP/6-31G(d,p) basis sets have been used to examine the structural and electronic properties of boron nitride (BN) diamantane interacted with the drug hydroxyurea (HU) as an anticancer drug. The findings have been shown that there is a decrease in the total energy after combining the drug with diamantane. The energy levels of HOMO and LUMO analyses indicate that the value of HOMO energy increased slightly, while the value of LUMO energy decreased significantly in these systems in the HU/BN diamantane. In addition, the decreasing of the energy gap between HOMO and LUMO confirms a strong bond between the drug hydroxyurea and BN diamantane. Finally, the drug's stability and reactivity with BN diamantane were investigated by measuring chemical reaction characteristics such as chemical potential, electron affinity, global hardness, and electrophilicity index. As a result, the nanocrystal of BN diamantane can be considered a vector for the delivery of anticancer drugs within biological systems.
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Pham DT, Tiyaboonchai W. Fibroin nanoparticles: a promising drug delivery system. Drug Deliv 2020; 27:431-448. [PMID: 32157919 PMCID: PMC7144220 DOI: 10.1080/10717544.2020.1736208] [Citation(s) in RCA: 83] [Impact Index Per Article: 16.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 02/20/2020] [Accepted: 02/25/2020] [Indexed: 01/13/2023] Open
Abstract
Fibroin is a dominant silk protein that possesses ideal properties as a biomaterial for drug delivery. Recently, the development of fibroin nanoparticles (FNPs) for various biomedical applications has been extensively studied. Due to their versatility and chemical modifiability, FNPs can encapsulate different types of therapeutic compounds, including small and big molecules, proteins, enzymes, vaccines, and genetic materials. Moreover, FNPs are able to be administered both parenterally and non-parenterally. This review summaries basic information on the silk and fibroin origin and characteristics, followed by the up-to-date data on the FNPs preparation and characterization methods. In addition, their medical applications as a drug delivery system are in-depth explored based on several administrative routes of parenteral, oral, transdermal, ocular, orthopedic, and respiratory. Finally, the challenges and suggested solutions, as well as the future outlooks of these systems are discussed.
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Affiliation(s)
- Duy Toan Pham
- Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
| | - Waree Tiyaboonchai
- Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand
- Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, The Center of Excellence for Innovation in Chemistry (PERCH-CIC), Mahidol University, Salaya, Thailand
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Indomethacin loaded dextran stearate polymeric micelles improve adjuvant-induced arthritis in rats: design and in vivo evaluation. Inflammopharmacology 2020; 29:107-121. [PMID: 33179175 DOI: 10.1007/s10787-020-00776-6] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 10/25/2020] [Indexed: 12/29/2022]
Abstract
BACKGROUND Indomethacin is a non-steroidal anti-inflammatory drug (NSAID) that can effectively control the pain and inflammation caused by rheumatoid arthritis (RA), but its usage is limited due to severe adverse effects. For this reason, making more specific formulations of this drug can be considered. The aim of the present study was designing a novel nano-sized indomethacin delivery system. MATERIALS AND METHODS Indomethacin-loaded dextran stearate polymeric micelles were prepared by dialysis method. Particle size and zeta potential of micelles were measured by a zeta sizer instrument. Drug release from micelles was investigated in phosphate buffer medium pH 7.4 and then the best formulation regarding physical properties and drug release was selected for animal studies. Arthritis was induced by complete Freund's adjuvant injection in rats. Then, the animals were randomly assigned into the model, the indomethacin solution and the polymeric micelles groups. The clinical effects of polymeric micelle formulation were assessed by measuring arthritis index, animal paw edema and measuring biochemical parameters including myeloperoxidase (MPO) activity, lipid peroxidation (LPO), glutathione (GSH), total antioxidant capacity (TAC), TNF-α, IL-17 and IL-1β. RESULTS Paw edema was attenuated following the administration of indomethacin-loaded polymeric micelles. Based on the findings of the present study, the use of indomethacin-loaded polymeric micelles could improve inflammatory symptoms, decrease arthritis index and decrease the diameter of the paw in arthritic rats in a significant manner (p ≤ 0.05). In addition, the use of polymeric micelles like indomethacin solution significantly reduced (p ≤ 0.05) the activity of MPO, LPO, TNF-α, IL-17 and IL-1β, and made a significant increase (p ≤ 0.05) in glutathione and TAC content and ameliorated structural changes in the paw tissue compared to the control group. CONCLUSION Our findings demonstrated that indomethacin-loaded dextran stearate polymeric micelles can provide more effective therapeutic effects in control of inflammation in arthritis in rat.
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40
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Karabasz A, Bzowska M, Szczepanowicz K. Biomedical Applications of Multifunctional Polymeric Nanocarriers: A Review of Current Literature. Int J Nanomedicine 2020; 15:8673-8696. [PMID: 33192061 PMCID: PMC7654520 DOI: 10.2147/ijn.s231477] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Accepted: 10/06/2020] [Indexed: 12/14/2022] Open
Abstract
Polymeric nanomaterials have become a prominent area of research in the field of drug delivery. Their application in nanomedicine can improve bioavailability, pharmacokinetics, and, therefore, the effectiveness of various therapeutics or contrast agents. There are many studies for developing new polymeric nanocarriers; however, their clinical application is somewhat limited. In this review, we present new complex and multifunctional polymeric nanocarriers as promising and innovative diagnostic or therapeutic systems. Their multifunctionality, resulting from the unique chemical and biological properties of the polymers used, ensures better delivery, and a controlled, sequential release of many different therapeutics to the diseased tissue. We present a brief introduction of the classical formulation techniques and describe examples of multifunctional nanocarriers, whose biological assessment has been carried out at least in vitro. Most of them, however, also underwent evaluation in vivo on animal models. Selected polymeric nanocarriers were grouped depending on their medical application: anti-cancer drug nanocarriers, nanomaterials delivering compounds for cancer immunotherapy or regenerative medicine, components of vaccines nanomaterials used for topical application, and lifestyle diseases, ie, diabetes.
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Affiliation(s)
- Alicja Karabasz
- Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland
| | - Monika Bzowska
- Department of Cell Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland
| | - Krzysztof Szczepanowicz
- Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Kraków, Poland
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Ferreira LM, Sari MHM, Cervi VF, Prado VC, Nadal JM, Azambuja JH, da Silveira EF, Nogueira CW, Farago PV, Braganhol E, Cruz L. Design of Pegylated-Nanocapsules to Diphenyl Diselenide Administration: In Vitro Evidence of Hemocompatible and Selective Antiglioma Formulation. AAPS PharmSciTech 2020; 21:307. [PMID: 33151442 DOI: 10.1208/s12249-020-01845-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Accepted: 10/07/2020] [Indexed: 12/31/2022] Open
Abstract
Diphenyl diselenide [(PhSe)2] is a pleiotropic pharmacological agent, but it has low aqueous solubility. The nanoencapsulation of (PhSe)2 allowed the preparation of an aqueous formulation as well as potentiated its in vitro antitumor effect and the effectiveness in a preclinical model of glioblastoma when administered by the intragastric route. Thus, aiming at maximizing the therapeutic potential of (PhSe)2, the present study designed a pegylated-formulation intending to intravenous administration of the (PhSe)2 as a new approach for glioma therapy. The poly(Ɛ-caprolactone) nanocapsules containing (PhSe)2 were physically coated with polyethyleneglycol (PEG) using the preformed polymer interfacial deposition technique and evaluated through physicochemical, morphological, spectroscopic, and thermal characteristics. Hemocompatibility was determined by the in vitro hemolysis test and cytotoxicity assays were performed in astrocytes and glioma C6 cells (10-100 μM). The pegylated-nanocapsules had an average diameter of 218 ± 25 nm, polydispersity index of 0.164 ± 0.046, zeta potential of - 8.1 ± 1.6 mV, pH 6.0 ± 0.09, (PhSe)2 content of 102.00 ± 3.57%, and encapsulation efficiency around 98%. Besides, the (PhSe)2 pegylated-nanocapsules were spherical, presented absence of chemical interaction among the constituents, and showed higher thermal stability than the non-encapsulated materials. PEG-coated nanocapsules did not cause hemolytic effect while formulations without PEG induced a hemolysis rate above 10%. Moreover, pegylated-nanocapsules had superior in vitro antiglioma effect in comparison to free compound (IC50: 24.10 μM and 74.83 μM, respectively). Therefore, the (PhSe)2-loaded pegylated-nanocapsule suspensions can be considered a hemocompatible formulation for the glioma treatment by the intravenous route.
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Patel AS, Lakshmibalasubramaniam S, Nayak B, Tripp C, Kar A, Sappati PK. Improved stability of phycobiliprotein within liposome stabilized by polyethylene glycol adsorbed cellulose nanocrystals. Int J Biol Macromol 2020; 163:209-218. [DOI: 10.1016/j.ijbiomac.2020.06.262] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 06/19/2020] [Accepted: 06/26/2020] [Indexed: 01/21/2023]
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Demir E. A review on nanotoxicity and nanogenotoxicity of different shapes of nanomaterials. J Appl Toxicol 2020; 41:118-147. [PMID: 33111384 DOI: 10.1002/jat.4061] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 08/15/2020] [Accepted: 08/18/2020] [Indexed: 12/16/2022]
Abstract
Nanomaterials (NMs) generally display fascinating physical and chemical properties that are not always present in bulk materials; therefore, any modification to their size, shape, or coating tends to cause significant changes in their chemical/physical and biological characteristics. The dramatic increase in efforts to use NMs renders the risk assessment of their toxicity highly crucial due to the possible health perils of this relatively uncharted territory. The different sizes and shapes of the nanoparticles are known to have an impact on organisms and an important place in clinical applications. The shape of nanoparticles, namely, whether they are rods, wires, or spheres, is a particularly critical parameter to affect cell uptake and site-specific drug delivery, representing a significant factor in determining the potency and magnitude of the effect. This review, therefore, intends to offer a picture of research into the toxicity of different shapes (nanorods, nanowires, and nanospheres) of NMs to in vitro and in vivo models, presenting an in-depth analysis of health risks associated with exposure to such nanostructures and benefits achieved by using certain model organisms in genotoxicity testing. Nanotoxicity experiments use various models and tests, such as cell cultures, cores, shells, and coating materials. This review article also attempts to raise awareness about practical applications of NMs in different shapes in biology, to evaluate their potential genotoxicity, and to suggest approaches to explain underlying mechanisms of their toxicity and genotoxicity depending on nanoparticle shape.
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Affiliation(s)
- Eşref Demir
- Vocational School of Health Services, Department of Medical Services and Techniques, Medical Laboratory Techniques Programme, Antalya Bilim University, Dosemealti, Antalya, Turkey
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Patil V, Patel A. Biodegradable Nanoparticles: A Recent Approach and Applications. Curr Drug Targets 2020; 21:1722-1732. [PMID: 32938346 DOI: 10.2174/1389450121666200916091659] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 07/14/2020] [Accepted: 07/22/2020] [Indexed: 11/22/2022]
Abstract
Biodegradable nanoparticles (NPs) are the novel carriers for the administration of drug molecules. Biodegradable nanoparticles have become popular recently because of their special features such as targeted delivery of drugs, improved bioavailability, and better therapeutic effectiveness to administer the drug at a constant rate. Polymeric NPs are very small-sized polymeric colloidal elements in which a drug of interest may be encapsulated or incorporated in their polymeric network or conjugated or adsorbed on the layer. Various polymers are employed in the manufacturing of nanoparticles, some of the frequently employed polymers are agents, chitosan, cellulose, gelatin, gliadin, polylactic acid, polylactic-co-glycolic acid, and pullulan. Nanoparticles have been progressively explored for the delivery of targeted ARVs to cells of HIV-infected and have performed the prolonged kinetic release. Drug embedded in this system can give better effectiveness, diminished resistance of drugs, reduction in systemic toxicity and symptoms, and also enhanced patient compliance. The present review highlights the frequently employed manufacturing methods for biodegradable nanoparticles, various polymers used, and its application in anti-retroviral therapy. Also, common evaluation parameters to check the purity of nanoparticles, ongoing and recently concluded clinical trials and patents filled by the various researchers, and the future implication of biodegradable NPs in an innovative drug delivery system are described. The biodegradable NPs are promising systems for the administration of a broad variety of drugs including anti-retroviral drugs, and hence biodegradable nanoparticles can be employed in the future for the treatment of several diseases and disorders.
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Affiliation(s)
- Vijay Patil
- Department of Pharmaceutics, Faculty of Pharmacy, Parul institute of Pharmacy, Parul University P.O.Limda, Ta.Waghodia, Vadodara, Gujarat 391760 Gujarat, India
| | - Asha Patel
- Department of Pharmaceutics, Faculty of Pharmacy, Parul institute of Pharmacy, Parul University P.O.Limda, Ta.Waghodia, Vadodara, Gujarat 391760 Gujarat, India
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Bruinsmann FA, Buss JH, Souto GD, Schultze E, de Cristo Soares Alves A, Seixas FK, Collares TV, Pohlmann AR, Guterres SS. Erlotinib-Loaded Poly(ε-Caprolactone) Nanocapsules Improve In Vitro Cytotoxicity and Anticlonogenic Effects on Human A549 Lung Cancer Cells. AAPS PharmSciTech 2020; 21:229. [PMID: 32778976 DOI: 10.1208/s12249-020-01723-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 06/03/2020] [Indexed: 12/15/2022] Open
Abstract
Lung cancer is the most frequent type of cancer and the leading cause of cancer-related mortality worldwide. This study aimed to develop erlotinib (ELB)-loaded poly(ε-caprolactone) nanocapsules (NCELB) and evaluated their in vitro cytotoxicity in A549 cells. The formulation was characterized in relation to hydrodynamic diameter (171 nm), polydispersity index (0.076), zeta potential (- 8 mV), drug content (0.5 mg.mL-1), encapsulation efficiency (99%), and pH (6.0). NCELB presented higher cytotoxicity than ELB in solution against A549 cells in the MTT and LIVE/DEAD cell viability assays after 24 h of treatment. The main mechanism of cytotoxicity of NCELB was the induction of apoptosis in A549 cells. Further, a significant decrease in A549 colony formation was verified after NCELB treatment in comparison with the unencapsulated drug treatment. The reduction in clonogenic capacity is very relevant as it can reduce the risk of tumor recurrence and metastasis. In conclusion, erlotinib-loaded PCL nanocapsules are promising nanoparticles carriers to increase the efficacy of ELB in lung cancer treatment.
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Mohammady M, Mohammadi Y, Yousefi G. Freeze-Drying of Pharmaceutical and Nutraceutical Nanoparticles: The Effects of Formulation and Technique Parameters on Nanoparticles Characteristics. J Pharm Sci 2020; 109:3235-3247. [PMID: 32702373 DOI: 10.1016/j.xphs.2020.07.015] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/23/2020] [Accepted: 07/15/2020] [Indexed: 12/12/2022]
Abstract
Nanoparticles (NPs) are of the most interesting novel vehicles for effective drug delivery to humans. Freeze drying is known as an engaging process to improve the long lasting stability of NPs formulations. This study aims to elucidate the importance of various parameters involving in freeze-drying of the most common pharmaceutical/nutraceutical NPs including nanosuspensions, nanocrystals (NCs), cocrystals/nanococrystals, nanoemulsions (NEs), nanocapsules (NCPs) and nanospheres (NSPs). Regarding this, the therapeutic goals of NPs and specifications of drug must be considered. According to our survey, the most influential factors for achieving optimum results include type and concentration of cryoprotectant/lyoprotectant, stabilizer structure and concentration, the NPs concentration in solution, freezing, annealing, and drying rate, the interaction between protectants and stabilizer, solvent type and antisolvent to solvent ratio. The study shows that for each class of NPs, specific variables are of highest significance and should be optimized. For instance, about NCs, freezing rate and antisolvent/solvent ratio should be particularly considered and for emulsified NPs, the best results have been obtained by 5-20% of saccharides as cryoprotectants. These findings suggest that to obtain a product with the lowest aggregation and particle size (PS), optimization of the effective factors in formulation and lyophilization process are essential.
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Affiliation(s)
- Mohsen Mohammady
- Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran
| | - Yasaman Mohammadi
- Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran
| | - Gholamhossein Yousefi
- Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, P.O. Box 71345-1583, Shiraz, Iran; Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran.
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Liu G, Xu X, Jiang L, Ji H, Zhu F, Jin B, Han J, Dong X, Yang F, Li B. Targeted Antitumor Mechanism of C-PC/CMC-CD55sp Nanospheres in HeLa Cervical Cancer Cells. Front Pharmacol 2020; 11:906. [PMID: 32636744 PMCID: PMC7319041 DOI: 10.3389/fphar.2020.00906] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 06/03/2020] [Indexed: 12/20/2022] Open
Abstract
In vitro studies had shown that C-Phycocyanin (C-PC) inhibited cervical cancer HeLa cells growth. We constructed C-PC/CMC-CD55sp nanospheres using C-PC, Carboxymethyl Chitosan (CMC), and CD55 ligand peptide (CD55sp) to allow for targeted antitumor effects against HeLa cells in vitro and in vivo. The characteristics of the nanospheres were determined using FTIR, electron microscopy, and laser particle size analysis. Flow cytometry, laser confocal microscopy and small animal imaging system showed the targeting of C-PC/CMC-CD55sp nanospheres on HeLa cells. Subsequently, the proliferation and apoptosis were analyzed by Cell Counting Kit-8 (CCK-8), flow cytometry, TUNEL assay and electron microscopy. The expression of the apoptosis-related protein was determined using western blot. The stainings of Hematoxylin and Eosin (HE) were employed to evaluate the cell condition of tumor tissue sections. The cytokines in the blood in tumor-bearing nude mice was determined using ELISA. These results showed that C-PC/CMC-CD55sp nanospheres were successfully constructed and targeted HeLa cells. The constructed nanospheres were more effective than C-PC alone in inhibiting the proliferation and inducing apoptosis in HeLa cells. We also found that C-PC/CMC-CD55sp nanospheres had a significant inhibitory effect on the expression of antiapoptotic protein Bcl-2 and a promotion on the transformation of caspase 3 to cleaved caspase 3. C-PC/CMC-CD55sp nanospheres played an important role in tumor suppression, reduced the expression TGF-β, and increased IL-6 and TNF-α. This study demonstrates that the constructed new C-PC/CMC-CD55sp nanospheres exerted targeted antitumor effects in vivo and in vitro which provided a novel idea for application of C-PC, and provided experimental basis for comprehensive targeted treatment of tumors.
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Affiliation(s)
- Guoxiang Liu
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Xiaohui Xu
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Liangqian Jiang
- Department of Medical Genetics, Linyi People's Hospital, Linyi, China
| | - Huanhuan Ji
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Feng Zhu
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Bingnan Jin
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Jingjing Han
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Xiaolei Dong
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Fanghao Yang
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China
| | - Bing Li
- Department of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, China.,Department of Hematology, The Affiliated Hospital of Qingdao University, Qingdao, China
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Shinde M, Bali N, Rathod S, Karemore M, Salve P. Effect of binary combinations of solvent systems on permeability profiling of pure agomelatine across rat skin: a comparative study with statistically optimized polymeric nanoparticles. Drug Dev Ind Pharm 2020; 46:826-845. [DOI: 10.1080/03639045.2020.1757697] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Mahesh Shinde
- University Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, India
| | - Nikhil Bali
- University Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, India
| | - Shahadev Rathod
- University Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, India
| | - Megha Karemore
- University Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, India
| | - Pramod Salve
- University Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, India
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Li Q, Li X, Zhao C. Strategies to Obtain Encapsulation and Controlled Release of Small Hydrophilic Molecules. Front Bioeng Biotechnol 2020; 8:437. [PMID: 32478055 PMCID: PMC7237580 DOI: 10.3389/fbioe.2020.00437] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 04/16/2020] [Indexed: 12/03/2022] Open
Abstract
The therapeutic effect of small hydrophilic molecules is limited by the rapid clearance from the systemic circulation or a local site of administration. The unsuitable pharmacokinetics and biodistribution can be improved by encapsulating them in drug delivery systems. However, the high-water solubility, very hydrophilic nature, and low molecular weight make it difficult to encapsulate small hydrophilic molecules in many drug delivery systems. In this mini-review, we highlight three strategies to efficiently encapsulate small hydrophilic molecules and achieve controlled release: physical encapsulation in micro/nanocapsules, physical adsorption via electronic interactions, and covalent conjugation. The principles, advantages, and disadvantages of each strategy are discussed. This review paper could be a guide for scientists, engineers, and medical doctors who want to improve the therapeutic efficacy of small hydrophilic drugs.
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Affiliation(s)
| | | | - Chao Zhao
- Department of Chemical and Biological Engineering, The University of Alabama, Tuscaloosa, AL, United States
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Deng S, Gigliobianco MR, Censi R, Di Martino P. Polymeric Nanocapsules as Nanotechnological Alternative for Drug Delivery System: Current Status, Challenges and Opportunities. NANOMATERIALS 2020; 10:nano10050847. [PMID: 32354008 PMCID: PMC7711922 DOI: 10.3390/nano10050847] [Citation(s) in RCA: 129] [Impact Index Per Article: 25.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 04/21/2020] [Accepted: 04/23/2020] [Indexed: 12/11/2022]
Abstract
Polymer-based nanocapsules have been widely studied as a potential drug delivery system in recent years. Nanocapsules-as one of kind nanoparticle-provide a unique nanostructure, consisting of a liquid/solid core with a polymeric shell. This is of increasing interest in drug delivery applications. In this review, nanocapsules delivery systems studied in last decade are reviewed, along with nanocapsule formulation, characterizations of physical/chemical/biologic properties and applications. Furthermore, the challenges and opportunities of nanocapsules applications are also proposed.
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