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Akhmetova DR, Rogova A, Tishchenko YA, Mitusova KA, Postovalova AS, Dovbysh OV, Gavrilova NV, Epifanovskaya OS, Pyatiizbyantsev TA, Shakirova AI, Brodskaia AV, Shipilovskikh SA, Timin AS. An investigation of nano- and micron-sized carriers based on calcium carbonate and polylactic acid for oral administration of siRNA. Expert Opin Drug Deliv 2024; 21:1279-1295. [PMID: 39141571 DOI: 10.1080/17425247.2024.2393244] [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: 01/10/2024] [Revised: 08/09/2024] [Accepted: 08/12/2024] [Indexed: 08/16/2024]
Abstract
BACKGROUND Oral delivery of small interfering RNAs (siRNAs) draws significant attention, but the gastrointestinal tract (GIT) has many biological barriers that limit the drugs' bioavailability. The aim of this work was to investigate the potential of micro- and nano-sized CaCO3 and PLA carriers for oral delivery of siRNA and reveal a relationship between the physicochemical features of these carriers and their biodistribution. RESEARCH DESIGN AND METHODS In vitro stability of carriers was investigated in simulated gastric and intestinal fluids. Toxicity and cellular uptake were investigated on Caco-2 cells. The biodistribution profiles of the developed CaCO3 and PLA carriers were examined using different visualization methods, including SPECT, fluorescence imaging, radiometry, and histological analysis. The delivery efficiency of siRNA loaded carriers was investigated both in vitro and in vivo. RESULTS Micro-sized carriers were accumulated in the stomach and later localized in the colon tissues. The nanoscale particles (100-250 nm) were distributed in the colon tissues. nPLA was also detected in small intestine. The developed carriers can prevent siRNA from premature degradation in GIT media. CONCLUSION Our results reveal how the physicochemical properties of the particles, including their size and material type can affect their biodistribution profile and oral delivery of siRNA.
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Affiliation(s)
- Darya R Akhmetova
- Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia
- International Research and Education Centre for Physics of Nanostructures, ITMO University, St. Petersburg, Russia
| | - Anna Rogova
- Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia
| | - Yulia A Tishchenko
- Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia
| | - Ksenia A Mitusova
- Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia
| | - Alisa S Postovalova
- Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia
| | - Olesya V Dovbysh
- Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia
| | - Nina V Gavrilova
- Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia
- Smorodintsev Research Institute of Influenza, Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia
| | - Olga S Epifanovskaya
- Laboratory of gene and cell therapy, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
| | - Timofey A Pyatiizbyantsev
- Laboratory of gene and cell therapy, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
| | - Alena I Shakirova
- Laboratory of gene and cell therapy, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
| | - Alexandra V Brodskaia
- Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia
- Smorodintsev Research Institute of Influenza, Ministry of Healthcare of the Russian Federation, St. Petersburg, Russia
| | - Sergei A Shipilovskikh
- International Research and Education Centre for Physics of Nanostructures, ITMO University, St. Petersburg, Russia
| | - Alexander S Timin
- Laboratory of nano- and microencapsulation of biologically active substances, Peter The Great St. Petersburg Polytechnic University, St. Petersburg, Russia
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Lim B, Kim KS, Ahn JY, Na K. Overcoming antibiotic resistance caused by genetic mutations of Helicobacter pylori with mucin adhesive polymer-based therapeutics. Biomaterials 2024; 308:122541. [PMID: 38547832 DOI: 10.1016/j.biomaterials.2024.122541] [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: 10/31/2023] [Revised: 02/22/2024] [Accepted: 03/19/2024] [Indexed: 05/03/2024]
Abstract
Herein, we describe the 3'-sialyllactose-polyethyleneimine-chlorine e6 conjugate (3PC), meticulously engineered to effectively target Helicobacter bacteria (H. pylori) within the gastric environment. The composition of 3PC comprises polyethyleneimine, a cationic polymer, 3'-sialyllactose, which exhibits a specific binding affinity for H. pylori surface proteins, and a photosensitizer capable of generating oxygen radicals in response to specific wavelengths. The distinctive feature of 3PC lies in its capacity to enhance interaction with the anionic mucus layer facilitated by electrostatic forces. This interaction results in prolonged residence within the intestinal environment. The extended vacation in the intestinal milieu overcomes inherent limitations that have historically impeded conventional antibiotics from efficiently reaching and targeting H. pylori. 3PC can be harnessed as a potent tool for antibacterial photodynamic therapy, and its versatility extends to addressing the challenges posed by various antibiotic-resistant strains. The exceptional efficacy of 3PC in enhancing intestinal residence time and eradicating H. pylori has been robustly substantiated in animal models, particularly in mice. In summary, 3PC is a formidable agent capable of eradicating H. pylori, irrespective of its antibiotic resistance status, by efficiently penetrating and selectively targeting the mucus layer within the gastric environment.
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Affiliation(s)
- Byoungjun Lim
- Department of BioMedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea
| | - Kyoung Sub Kim
- Department of BioMedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea
| | - Ji Yong Ahn
- Department of Gastroenterology, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, Republic of Korea
| | - Kun Na
- Department of BioMedical-Chemical Engineering, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea; Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do, 14662, Republic of Korea.
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Dubashynskaya NV, Petrova VA, Skorik YA. Biopolymer Drug Delivery Systems for Oromucosal Application: Recent Trends in Pharmaceutical R&D. Int J Mol Sci 2024; 25:5359. [PMID: 38791397 PMCID: PMC11120705 DOI: 10.3390/ijms25105359] [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: 04/21/2024] [Revised: 05/10/2024] [Accepted: 05/13/2024] [Indexed: 05/26/2024] Open
Abstract
Oromucosal drug delivery, both local and transmucosal (buccal), is an effective alternative to traditional oral and parenteral dosage forms because it increases drug bioavailability and reduces systemic drug toxicity. The oral mucosa has a good blood supply, which ensures that drug molecules enter the systemic circulation directly, avoiding drug metabolism during the first passage through the liver. At the same time, the mucosa has a number of barriers, including mucus, epithelium, enzymes, and immunocompetent cells, that are designed to prevent the entry of foreign substances into the body, which also complicates the absorption of drugs. The development of oromucosal drug delivery systems based on mucoadhesive biopolymers and their derivatives (especially thiolated and catecholated derivatives) is a promising strategy for the pharmaceutical development of safe and effective dosage forms. Solid, semi-solid and liquid pharmaceutical formulations based on biopolymers have several advantageous properties, such as prolonged residence time on the mucosa due to high mucoadhesion, unidirectional and modified drug release capabilities, and enhanced drug permeability. Biopolymers are non-toxic, biocompatible, biodegradable and may possess intrinsic bioactivity. A rational approach to the design of oromucosal delivery systems requires an understanding of both the anatomy/physiology of the oral mucosa and the physicochemical and biopharmaceutical properties of the drug molecule/biopolymer, as presented in this review. This review summarizes the advances in the pharmaceutical development of mucoadhesive oromucosal dosage forms (e.g., patches, buccal tablets, and hydrogel systems), including nanotechnology-based biopolymer nanoparticle delivery systems (e.g., solid lipid particles, liposomes, biopolymer polyelectrolyte particles, hybrid nanoparticles, etc.).
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Affiliation(s)
| | | | - Yury A. Skorik
- Institute of Macromolecular Compounds of the Russian Academy of Sciences, Bolshoi VO 31, 199004 St. Petersburg, Russia
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Parmentier L, D'Haese S, Duquesne J, Bray F, Van der Meeren L, Skirtach AG, Rolando C, Dmitriev RI, Van Vlierberghe S. 2D fibrillar osteoid niche mimicry through inclusion of visco-elastic and topographical cues in gelatin-based networks. Int J Biol Macromol 2024; 254:127619. [PMID: 37898251 DOI: 10.1016/j.ijbiomac.2023.127619] [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: 06/18/2023] [Revised: 10/10/2023] [Accepted: 10/20/2023] [Indexed: 10/30/2023]
Abstract
Given the clinical need for osteoregenerative materials incorporating controlled biomimetic and biophysical cues, a novel highly-substituted norbornene-modified gelatin was developed enabling thiol-ene crosslinking exploiting thiolated gelatin as cell-interactive crosslinker. Comparing the number of physical crosslinks, the degree of hydrolytic degradation upon modification, the network density and the chemical crosslinking type, the osteogenic effect of visco-elastic and topographical properties was evaluated. This novel network outperformed conventional gelatin-based networks in terms of osteogenesis induction, as evidenced in 2D dental pulp stem cell seeding assays, resulting from the presentation of both a local (substrate elasticity, 25-40 kPa) and a bulk (compressive modulus, 25-45 kPa) osteogenic substrate modulus in combination with adequate fibrillar cell adhesion spacing to optimally transfer traction forces from the fibrillar ECM (as evidenced by mesh size determination with the rubber elasticity theory) and resulting in a 1.7-fold increase in calcium production (compared to the gold standard gelatin methacryloyl (GelMA)).
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Affiliation(s)
- Laurens Parmentier
- Polymer Chemistry and Biomaterials Group (PBM), Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Faculty of Sciences, Ghent University, Krijgslaan 281, 9000 Ghent, Belgium
| | - Sophie D'Haese
- Polymer Chemistry and Biomaterials Group (PBM), Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Faculty of Sciences, Ghent University, Krijgslaan 281, 9000 Ghent, Belgium
| | - Jessie Duquesne
- Polymer Chemistry and Biomaterials Group (PBM), Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Faculty of Sciences, Ghent University, Krijgslaan 281, 9000 Ghent, Belgium
| | - Fabrice Bray
- Miniaturisation pour la synthèse, l'analyse et la protéomique (MSAP), CNRS, Université de Lille, F-59000 Lille, France
| | - Louis Van der Meeren
- Nano-biotechnology Laboratory, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent university, Proeftuinstraat 86, 9000 Ghent, Belgium
| | - Andre G Skirtach
- Nano-biotechnology Laboratory, Department of Biotechnology, Faculty of Bioscience Engineering, Ghent university, Proeftuinstraat 86, 9000 Ghent, Belgium
| | - Christian Rolando
- Miniaturisation pour la synthèse, l'analyse et la protéomique (MSAP), CNRS, Université de Lille, F-59000 Lille, France
| | - Ruslan I Dmitriev
- Tissue Engineering and Biomaterials Group, Department of Human Structure and Repair, Faculty of Medical and Health Sciences, Ghent university, C. Heymanslaan 10, 9000 Ghent, Belgium
| | - Sandra Van Vlierberghe
- Polymer Chemistry and Biomaterials Group (PBM), Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Faculty of Sciences, Ghent University, Krijgslaan 281, 9000 Ghent, Belgium.
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Wang CM, Fernez MT, Woolston BM, Carrier RL. Native gastrointestinal mucus: Critical features and techniques for studying interactions with drugs, drug carriers, and bacteria. Adv Drug Deliv Rev 2023; 200:114966. [PMID: 37329985 PMCID: PMC11184232 DOI: 10.1016/j.addr.2023.114966] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 06/09/2023] [Accepted: 06/12/2023] [Indexed: 06/19/2023]
Abstract
Gastrointestinal mucus plays essential roles in modulating interactions between intestinal lumen contents, including orally delivered drug carriers and the gut microbiome, and underlying epithelial and immune tissues and cells. This review is focused on the properties of and methods for studying native gastrointestinal mucus and its interactions with intestinal lumen contents, including drug delivery systems, drugs, and bacteria. The properties of gastrointestinal mucus important to consider in its analysis are first presented, followed by a discussion of different experimental setups used to study gastrointestinal mucus. Applications of native intestinal mucus are then described, including experimental methods used to study mucus as a barrier to drug delivery and interactions with intestinal lumen contents that impact barrier properties. Given the significance of the microbiota in health and disease, its impact on drug delivery and drug metabolism, and the use of probiotics and microbe-based delivery systems, analysis of interactions of bacteria with native intestinal mucus is then reviewed. Specifically, bacteria adhesion to, motility within, and degradation of mucus is discussed. Literature noted is focused largely on applications of native intestinal mucus models as opposed to isolated mucins or reconstituted mucin gels.
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Affiliation(s)
- Chia-Ming Wang
- Department of Bioengineering, Northeastern University, Boston, MA, USA
| | - Matthew T Fernez
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA
| | - Benjamin M Woolston
- Department of Chemical Engineering, Northeastern University, Boston, MA, USA
| | - Rebecca L Carrier
- Department of Bioengineering, Northeastern University, Boston, MA, USA; Department of Chemical Engineering, Northeastern University, Boston, MA, USA; Department of Biology, Northeastern University, Boston, MA, USA.
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Sachdeva B, Sachdeva P, Negi A, Ghosh S, Han S, Dewanjee S, Jha SK, Bhaskar R, Sinha JK, Paiva-Santos AC, Jha NK, Kesari KK. Chitosan Nanoparticles-Based Cancer Drug Delivery: Application and Challenges. Mar Drugs 2023; 21:211. [PMID: 37103352 PMCID: PMC10142570 DOI: 10.3390/md21040211] [Citation(s) in RCA: 37] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 03/19/2023] [Accepted: 03/22/2023] [Indexed: 03/30/2023] Open
Abstract
Chitin is the second most abundant biopolymer consisting of N-acetylglucosamine units and is primarily derived from the shells of marine crustaceans and the cell walls of organisms (such as bacteria, fungi, and algae). Being a biopolymer, its materialistic properties, such as biodegradability, and biocompatibility, make it a suitable choice for biomedical applications. Similarly, its deacetylated derivative, chitosan, exhibits similar biocompatibility and biodegradability properties, making it a suitable support material for biomedical applications. Furthermore, it has intrinsic material properties such as antioxidant, antibacterial, and antitumor. Population studies have projected nearly 12 million cancer patients across the globe, where most will be suffering from solid tumors. One of the shortcomings of potent anticancer drugs is finding a suitable cellular delivery material or system. Therefore, identifying new drug carriers to achieve effective anticancer therapy is becoming essential. This paper focuses on the strategies implemented using chitin and chitosan biopolymers in drug delivery for cancer treatment.
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Affiliation(s)
- Bhuvi Sachdeva
- Department of Physics and Astrophysics, Bhagini Nivedita College, University of Delhi, Delhi 110072, India
| | - Punya Sachdeva
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, India
| | - Arvind Negi
- Department of Bioproducts and Biosystems, School of Chemical Engineering, Aalto University, 00076 Espoo, Finland
| | - Shampa Ghosh
- GloNeuro, Sector 107, Vishwakarma Road, Noida 201301, India
- ICMR—National Institute of Nutrition, Tarnaka, Hyderabad 500007, India
| | - Sungsoo Han
- School of Chemical Engineering, Yeungnam University, Gyeonsang 38541, Republic of Korea
- Research Institute of Cell Culture, Yeungnam University, 280 Daehak-Ro, Gyeongsan 38541, Republic of Korea
| | - Saikat Dewanjee
- Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India
| | - Saurabh Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India
- Department of Biotechnology Engineering & Food Technology, Chandigarh University, Mohali 140413, India
| | - Rakesh Bhaskar
- School of Chemical Engineering, Yeungnam University, Gyeonsang 38541, Republic of Korea
| | | | - Ana Cláudia Paiva-Santos
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
- REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Niraj Kumar Jha
- Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India
- Department of Biotechnology, School of Applied & Life Sciences (SALS), Uttaranchal University, Dehradun 248007, India
- School of Bioengineering & Biosciences, Lovely Professional University, Phagwara 144411, India
| | - Kavindra Kumar Kesari
- Department of Applied Physics, School of Science, Aalto University, 00076 Espoo, Finland
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Ahmady A, Abu Samah NH. A review: Gelatine as a bioadhesive material for medical and pharmaceutical applications. Int J Pharm 2021; 608:121037. [PMID: 34438009 DOI: 10.1016/j.ijpharm.2021.121037] [Citation(s) in RCA: 60] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 08/10/2021] [Accepted: 08/20/2021] [Indexed: 12/23/2022]
Abstract
Bioadhesive polymers offer versatility to medical and pharmaceutical inventions. The incorporation of such materials to conventional dosage forms or medical devices may confer or improve the adhesivity of the bioadhesive systems, subsequently prolonging their residence time at the site of absorption or action and providing sustained release of actives with improved bioavailability and therapeutic outcomes. For decades, much focus has been put on scientific works to replace synthetic polymers with biopolymers with desirable functional properties. Gelatine has been considered one of the most promising biopolymers. Despite its biodegradability, biocompatibility and unique biological properties, gelatine exhibits poor mechanical and adhesive properties, limiting its end-use applications. The chemical modification and blending of gelatine with other biomaterials are strategies proposed to improve its bioadhesivity. Here we discuss the classical approaches involving a variety of polymer blends and composite systems containing gelatine, and gelatine modifications via thiolation, methacrylation, catechol conjugation, amination and other newly devised strategies. We highlight several of the latest studies on these strategies and their relevant findings.
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Affiliation(s)
- Amina Ahmady
- Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi MARA, Selangor Branch, Puncak Alam Campus, 42300 Puncak Alam, Malaysia
| | - Nor Hayati Abu Samah
- Department of Pharmaceutics, Faculty of Pharmacy, Universiti Teknologi MARA, Selangor Branch, Puncak Alam Campus, 42300 Puncak Alam, Malaysia.
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Vrettos NN, Roberts CJ, Zhu Z. Gastroretentive Technologies in Tandem with Controlled-Release Strategies: A Potent Answer to Oral Drug Bioavailability and Patient Compliance Implications. Pharmaceutics 2021; 13:pharmaceutics13101591. [PMID: 34683884 PMCID: PMC8539558 DOI: 10.3390/pharmaceutics13101591] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2021] [Revised: 09/22/2021] [Accepted: 09/27/2021] [Indexed: 11/24/2022] Open
Abstract
There have been many efforts to improve oral drug bioavailability and therapeutic efficacy and patient compliance. A variety of controlled-release oral delivery systems have been developed to meet these needs. Gastroretentive drug delivery technologies have the potential to achieve retention of the dosage form in the upper gastrointestinal tract (GIT) that can be sufficient to ensure complete solubilisation of the drugs in the stomach fluids, followed by subsequent absorption in the stomach or proximal small intestine. This can be beneficial for drugs that have an “absorption window” or are absorbed to a different extent in various segments of the GIT. Therefore, gastroretentive technologies in tandem with controlled-release strategies could enhance both the therapeutic efficacy of many drugs and improve patient compliance through a reduction in dosing frequency. The paper reviews different gastroretentive drug delivery technologies and controlled-release strategies that can be combined and summarises examples of formulations currently in clinical development and commercially available gastroretentive controlled-release products. The different parameters that need to be considered and monitored during formulation development for these pharmaceutical applications are highlighted.
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Alrfooh A, Patel A, Laroia S. Transarterial Radioembolization Agents: a Review of the Radionuclide Agents and the Carriers. Nucl Med Mol Imaging 2021; 55:162-172. [PMID: 34422126 PMCID: PMC8322227 DOI: 10.1007/s13139-021-00709-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 06/16/2021] [Accepted: 06/29/2021] [Indexed: 11/30/2022] Open
Abstract
Liver tumors, both primary and secondary to metastatic disease, remain a major challenge, with an increasing incidence. In this context, taking advantage of the dual blood supply of the liver, and the fact that liver tumors derive majority of their blood supply from the hepatic artery, intraarterial therapies are gaining popularity. Intraarterial liver-directed therapy (IALDT) is the option when the surgery is not feasible due to the number of metastases or for other reasons. Transarterial radioembolization (TARE) is a specific type of IALDT, where a carrier particle/microsphere is labeled with a radioactive substance and then is injected into hepatic artery for therapeutic purposes. As this field is rapidly evolving, with multiple agents being investigated and being introduced into clinical practice, it is hard for the practitioners and researchers to encompass all the available information concisely. This article aims to present a comprehensive review of the prominent TARE technologies.
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Affiliation(s)
- Aysheh Alrfooh
- University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242 USA
| | - Aditi Patel
- Department of Radiology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242 USA
| | - Sandeep Laroia
- Department of Radiology, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242 USA
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Dong Z, Meng X, Yang W, Zhang J, Sun P, Zhang H, Fang X, Wang DA, Fan C. Progress of gelatin-based microspheres (GMSs) as delivery vehicles of drug and cell. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2021; 122:111949. [PMID: 33641932 DOI: 10.1016/j.msec.2021.111949] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 01/30/2021] [Accepted: 02/02/2021] [Indexed: 12/13/2022]
Abstract
Gelatin has various attractive features as biomedical materials, for instance, biocompatibility, low immunogenicity, biodegradability, and ease of manipulation. In recent years, various gelatin-based microspheres (GMSs) have been fabricated with innovative technologies to serve as sustained delivery vehicles of drugs and genetic materials as well as beneficial bacteria. Moreover, GMSs have exhibited promising potentials to act as both cell carriers and 3D scaffold components in tissue engineering and regenerative medicine, which not only exhibit excellent injectability but also could be integrated into a macroscale construct with the laden cells. Herein, we aim to thoroughly summarize the recent progress in the preparations and biomedical applications of GMSs and then to point out the research direction in future. First, various methods for the fabrication of GMSs will be described. Second, the recent use of GMSs in tumor embolization and in the delivery of cells, drugs, and genetic material as well as bacteria will be presented. Finally, several key factors that may enhance the improvement of GMSs were suggested as delivery vehicles.
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Affiliation(s)
- Zuoxiang Dong
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao 266000, Shandong, China; Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China
| | - Xinyue Meng
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao 266000, Shandong, China
| | - Wei Yang
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao 266000, Shandong, China
| | - Jinfeng Zhang
- Department of Surgery, Songshan Hospital of Qingdao University, Qingdao 266021, Shandong, China
| | - Peng Sun
- Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China
| | - Huawei Zhang
- Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China
| | - Xing Fang
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS 39216, USA
| | - Dong-An Wang
- Department of Biomedical Engineering, City University of Hong Kong, Kowloon, Hong Kong Special Administrative Region; Shenzhen Research Institute, City University of Hong Kong, Shenzhen Hi-tech Industrial Park, Shenzhen, Guangdong 518057, China; Karolinska Institute Ming Wai Lau Centre for Reparative Medicine, HKSTP, Sha Tin, Hong Kong Special Administrative Region.
| | - Changjiang Fan
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao 266000, Shandong, China.
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Ghorbani F, Zamanian A, Behnamghader A, Daliri Joupari M. Bioactive and biostable hyaluronic acid-pullulan dermal hydrogels incorporated with biomimetic hydroxyapatite spheres. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 112:110906. [DOI: 10.1016/j.msec.2020.110906] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 03/24/2020] [Accepted: 03/27/2020] [Indexed: 12/18/2022]
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John TS, Yadav PK, Kumar D, Singh SK, Hasan SH. Highly fluorescent carbon dots from wheat bran as a novel drug delivery system for bacterial inhibition. LUMINESCENCE 2020; 35:913-923. [DOI: 10.1002/bio.3801] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 02/12/2020] [Accepted: 03/06/2020] [Indexed: 12/20/2022]
Affiliation(s)
- Titto Sunil John
- Nano Material Research Laboratory, Department of ChemistryIndian Institute of Technology (BHU) Varanasi Uttar Pradesh India
| | - Pradeep Kumar Yadav
- Nano Material Research Laboratory, Department of ChemistryIndian Institute of Technology (BHU) Varanasi Uttar Pradesh India
| | - Devendra Kumar
- Department of Pharmaceutical Engineering and TechnologyIndian Institute of Technology (BHU) Varanasi Uttar Pradesh India
| | - Sushil Kumar Singh
- Department of Pharmaceutical Engineering and TechnologyIndian Institute of Technology (BHU) Varanasi Uttar Pradesh India
| | - Syed Hadi Hasan
- Nano Material Research Laboratory, Department of ChemistryIndian Institute of Technology (BHU) Varanasi Uttar Pradesh India
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Ghorbani F, Zamanian A. An efficient functionalization of dexamethasone-loaded polymeric scaffold with [3-(2,3-epoxypropoxy)-propyl]-trimethoxysilane coupling agent for bone regeneration: Synthesis, characterization, and in vitro evaluation. J BIOACT COMPAT POL 2020. [DOI: 10.1177/0883911520903761] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
In this study, dexamethasone-loaded gelatin–starch scaffolds were fabricated by the freeze-drying technique under different cooling temperatures and polymeric compositions. The constructs were modified via [3-(2,3-epoxypropoxy)-propyl]-trimethoxysilane coupling agent in order to produce a bioactive network structure for bone tissue engineering applications. Herein, the synergistic effect of [3-(2,3-epoxypropoxy)-propyl]-trimethoxysilane and dexamethasone was examined on the bioactivity and osteogenic behavior of scaffolds. Based on scanning electron microscopy micrographs, more fine pores were formed at higher freezing temperatures. The prepared microstructure at a rapid freezing rate resulted in diminished mechanical properties and a greater level of swelling and durability compared with a slow freezing rate. According to the acquired results, the mechanical strength decreased, while both absorption capacity and mass loss rate increased as a function of starch addition. Furthermore, the enhancement of hydrophilicity and reduction of mechanical stability enhanced the dexamethasone release levels. In addition, the synthesized constructs confirmed the positive effect of [3-(2,3-epoxypropoxy)-propyl]-trimethoxysilane and dexamethasone on biomimetic mineralization of the scaffolds. Supporting the cellular adhesion and proliferation alongside the expression of alkaline phosphatase, especially in the presence of dexamethasone, was the other advantage of synthetic scaffolds as a bone reconstructive substitute. Accordingly, drug-loaded hybrid constructs seem to be promising for further preclinical and clinical investigations in bone tissue engineering.
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Affiliation(s)
- Farnaz Ghorbani
- Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
| | - Ali Zamanian
- Department of Nanotechnology and Advanced Materials, Materials and Energy Research Center, Karaj, Islamic Republic of Iran
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14
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Maney V, Singh M. The Synergism of Platinum-Gold Bimetallic Nanoconjugates Enhances 5-Fluorouracil Delivery In Vitro. Pharmaceutics 2019; 11:pharmaceutics11090439. [PMID: 31480562 PMCID: PMC6781313 DOI: 10.3390/pharmaceutics11090439] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Revised: 07/29/2019] [Accepted: 08/01/2019] [Indexed: 02/07/2023] Open
Abstract
Nanoparticle application has significantly impacted the field of medicine. The need to develop novel drugs with higher therapeutic potential has stimulated the development of innovative delivery strategies to mitigate the potent side effects associated with known chemotherapeutic drugs. This paper describes the synthesis of platinum-gold bimetallic nanoparticles (PtAuBNps), their functionalisation with chitosan, and entrapment of the anticancer drug 5-fluorouracil (5-FU). All PtAuBNps and their drug nanocomposites were physico-chemically characterised, displaying desirable properties with regards to shape, size (<120 nm) and colloidal stability. 5-FU binding and loading capacities in PtAuBNps were found to be 90.17% and 22.56%, respectively. In vitro cytotoxicity profiles determined using the MTT and SRB assays reflected up to 65% cell death in the MCF-7, HepG2 and Caco-2 cell lines. These nanocomposites exhibited excellent physiochemical attributes, high specificity towards cancer cells, with a pH-sensitive drug release in a simulated acidic tumour microenvironment through zero-order release kinetics. In addition, they possessed the potential to traverse the mucosal lining facilitating oral drug administration. Overall, 5-FU encapsulation improved the bioavailability of the drug in cancer cells, with the promise of enhancing its therapeutic effect, biocompatibility and safety. These positive results highlight PtAuBNps as promising in vitro delivery systems and merits future in vivo research.
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Affiliation(s)
- Vareessh Maney
- Nano-Gene and Drug Delivery Group, Discipline of Biochemistry, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa
| | - Moganavelli Singh
- Nano-Gene and Drug Delivery Group, Discipline of Biochemistry, University of KwaZulu-Natal, Private Bag X54001, Durban, South Africa.
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15
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Garg U, Chauhan S, Nagaich U, Jain N. Current Advances in Chitosan Nanoparticles Based Drug Delivery and Targeting. Adv Pharm Bull 2019; 9:195-204. [PMID: 31380245 PMCID: PMC6664124 DOI: 10.15171/apb.2019.023] [Citation(s) in RCA: 256] [Impact Index Per Article: 42.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 01/11/2019] [Accepted: 04/13/2019] [Indexed: 01/08/2023] Open
Abstract
Nanoparticles (NPs) have been found to be potential targeted and controlled release drug delivery systems. Various drugs can be loaded in the NPs to achieve targeted delivery. Chitosan NPs being biodegradable, biocompatible, less toxic and easy to prepare, are an effective and potential tool for drug delivery. Chitosan is natural biopolymer which can be easily functionalized to obtain the desired targeted results and is also approved by GRAS (Generally Recognized as Safe by the United States Food and Drug Administration [US FDA]). Various methods for preparation of chitosan NPs include, ionic cross-linking, covalent cross-linking, reverse micellar method, precipitation and emulsion-droplet coalescence method. Chitosan NPs are found to have plethora of applications in drug delivery diagnosis and other biological applications. The key applications include ocular drug delivery, per-oral delivery, pulmonary drug delivery, nasal drug delivery, mucosal drug delivery, gene delivery, buccal drug delivery, vaccine delivery, vaginal drug delivery and cancer therapy. The present review describes the formation of chitosan, synthesis of chitosan NPs and their various applications in drug delivery.
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Affiliation(s)
| | | | | | - Neha Jain
- Amity Institute of Pharmacy, Amity University, Sector-125, Noida, Uttar Pradesh-201303
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16
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Tripathi J, Thapa P, Maharjan R, Jeong SH. Current State and Future Perspectives on Gastroretentive Drug Delivery Systems. Pharmaceutics 2019; 11:pharmaceutics11040193. [PMID: 31010054 PMCID: PMC6523542 DOI: 10.3390/pharmaceutics11040193] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 04/07/2019] [Accepted: 04/17/2019] [Indexed: 01/09/2023] Open
Abstract
In recent years, many attempts have been made to enhance the drug bioavailability and therapeutic effectiveness of oral dosage forms. In this context, various gastroretentive drug delivery systems (GRDDS) have been used to improve the therapeutic efficacy of drugs that have a narrow absorption window, are unstable at alkaline pH, are soluble in acidic conditions, and are active locally in the stomach. In this review, we discuss the physiological state of the stomach and various factors that affect GRDDS. Recently applied gastrointestinal technologies such as expandable, superporous hydrogel; bio/mucoadhesive, magnetic, ion-exchange resin; and low- and high-density-systems have also been examined along with their merits and demerits. The significance of in vitro and in vivo evaluation parameters of various GRDDS is summarized along with their applications. Moreover, future perspectives on this technology are discussed to minimize the gastric emptying rate in both the fasted and fed states. Overall, this review may inform and guide formulation scientists in designing the GRDDS.
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Affiliation(s)
- Julu Tripathi
- College of Pharmacy, Dongguk University-Seoul, 32 Donggukro, Ilsandonggu, Goyang, Gyeonggi 10326, Korea.
| | - Prakash Thapa
- College of Pharmacy, Dongguk University-Seoul, 32 Donggukro, Ilsandonggu, Goyang, Gyeonggi 10326, Korea.
| | - Ravi Maharjan
- College of Pharmacy, Dongguk University-Seoul, 32 Donggukro, Ilsandonggu, Goyang, Gyeonggi 10326, Korea.
| | - Seong Hoon Jeong
- College of Pharmacy, Dongguk University-Seoul, 32 Donggukro, Ilsandonggu, Goyang, Gyeonggi 10326, Korea.
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17
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Abruzzo A, Cerchiara T, Bigucci F, Zuccheri G, Cavallari C, Saladini B, Luppi B. Cromolyn-crosslinked chitosan nanoparticles for the treatment of allergic rhinitis. Eur J Pharm Sci 2019; 131:136-145. [PMID: 30771474 DOI: 10.1016/j.ejps.2019.02.015] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 02/04/2019] [Accepted: 02/11/2019] [Indexed: 12/31/2022]
Abstract
The aim of this work was to prepare new mucoadhesive nasal decongestant nanoparticles obtained by direct crosslinking between the cationic polymer chitosan and the anionic drug cromolyn. Different chitosan/cromolyn molar ratios were used in order to obtain nanoparticles of suitable size, encapsulation efficiency/drug loading and mucoadhesion. Moreover, the ability of the nanoparticles to deliver cromolyn into and through the nasal mucosa was evaluated. The obtained positively charged nanoparticles, sized 180-400 nm, showed interesting properties in terms of yield, mucoadhesion, encapsulation efficiency and drug loading. Release and permeation/penetration data indicated the ability of the nanoparticles to retain a high amount of cromolyn inside the mucosa, which is rich in mast cells. These findings suggest developing decongestant nanoparticles for potential treatment of allergic rhinitis.
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Affiliation(s)
- Angela Abruzzo
- Department of Pharmacy and Biotechnology, Via San Donato 19/2, University of Bologna, 40127 Bologna, Italy.
| | - Teresa Cerchiara
- Department of Pharmacy and Biotechnology, Via San Donato 19/2, University of Bologna, 40127 Bologna, Italy.
| | - Federica Bigucci
- Department of Pharmacy and Biotechnology, Via San Donato 19/2, University of Bologna, 40127 Bologna, Italy.
| | - Giampaolo Zuccheri
- Department of Pharmacy and Biotechnology, Via Irnerio 48, University of Bologna, 40126 Bologna, Italy.
| | - Cristina Cavallari
- Department of Pharmacy and Biotechnology, Via San Donato 15, University of Bologna, 40127 Bologna, Italy.
| | - Bruno Saladini
- PolyCrystalline s.r.l., Via F.S. Fabbri 127/1, 40059, Medicina, Bologna, Italy.
| | - Barbara Luppi
- Department of Pharmacy and Biotechnology, Via San Donato 19/2, University of Bologna, 40127 Bologna, Italy.
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18
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Çelebioğlu HY, Lee S, Chronakis IS. Interactions of salivary mucins and saliva with food proteins: a review. Crit Rev Food Sci Nutr 2019; 60:64-83. [PMID: 30632771 DOI: 10.1080/10408398.2018.1512950] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Mucins are long glycoprotein molecules responsible for the gel nature of the mucous layer that covers epithelial surfaces throughout the body. Mucins, as the major salivary proteins, are also important proteins for the food oral processing and digestion. The interactions of salivary mucins and saliva with several food proteins and food protein emulsions, as well as their functional properties related to the food oral processing were reviewed in this paper. The target food proteins of focus were whey proteins (lactoferrin and beta-lactoglobulin) and non-whey proteins (casein, gelatin, galectin/lectin, and proline-rich proteins). Most of the studies suggest that electrostatic attraction (between positively charged food proteins with negatively charged moieties of mucin mainly on glycosylated region of mucin) is the major mode of interaction between them. On the other hand, casein attracts the salivary proteins only via non-covalent interactions due to its naturally self-assembled micellar structure. Moreover, recent studies related to β-lactoglobulin (BLG)-mucin interactions have clarified the importance of hydrophobic as well as hydrophilic interactions, such as hydrogen bonding. Furthermore, in vitro studies between protein emulsions and saliva observed a strong aggregating effect of saliva on caseinate and whey proteins as well as on surfactant-stabilized emulsions. Besides, the sign and the density of the charge on the surface of the protein emulsion droplets contribute significantly to the behavior of the emulsion when mixed with saliva. Other studies also suggested that the interactions between saliva and whey proteins depends on the pH in addition to the flow rate of the saliva. Overall, the role of interactions of food proteins and food protein emulsions with mucin/saliva-proteins in the oral perception, as well as the physicochemical and structural changes of proteins were discussed.
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Affiliation(s)
- Hilal Y Çelebioğlu
- Nano-BioScience Research Group, DTU-Food, Technical University of Denmark, Lyngby, Denmark
| | - Seunghwan Lee
- Department of Mechanical Engineering, Technical University of Denmark, Lyngby, Denmark
| | - Ioannis S Chronakis
- Nano-BioScience Research Group, DTU-Food, Technical University of Denmark, Lyngby, Denmark
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19
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Fabrication of lecithin-gum tragacanth muco-adhesive hybrid nano-carrier system for in-vivo performance of Amphotericin B. Carbohydr Polym 2018; 194:89-96. [DOI: 10.1016/j.carbpol.2018.04.013] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 04/02/2018] [Accepted: 04/03/2018] [Indexed: 02/02/2023]
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20
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Ghorbani F, Zamanian A, Behnamghader A, Daliri Joupari M. A novel pathway for in situ
synthesis of modified gelatin microspheres by silane coupling agents as a bioactive platform. J Appl Polym Sci 2018. [DOI: 10.1002/app.46739] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Farnaz Ghorbani
- Department of Biomedical Engineering, Science and Research Branch; Islamic Azad University; P.O. Box 4515-775 Tehran Iran
| | - Ali Zamanian
- Department of Nanotechnology and Advanced Materials; Materials and Energy Research Center; P.O. Box 14155-4777 Karaj Iran
| | - Aliasghar Behnamghader
- Department of Nanotechnology and Advanced Materials; Materials and Energy Research Center; P.O. Box 14155-4777 Karaj Iran
| | - Morteza Daliri Joupari
- Department of Animal, Avian and Marine Biotechnology; National Institute of Genetic Engineering and Biotechnology; P.O. Box 14965-161 Tehran Iran
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21
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Mackie AR, Goycoolea FM, Menchicchi B, Caramella CM, Saporito F, Lee S, Stephansen K, Chronakis IS, Hiorth M, Adamczak M, Waldner M, Nielsen HM, Marcelloni L. Innovative Methods and Applications in Mucoadhesion Research. Macromol Biosci 2017; 17. [DOI: 10.1002/mabi.201600534] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2016] [Revised: 02/10/2017] [Indexed: 01/03/2023]
Affiliation(s)
- Alan R. Mackie
- Institute of Food Research; Norwich Research Park Norwich NR4 7UA UK
- School of Food Science and Nutrition; University of Leeds; LS2 9JT Leeds UK
| | - Francisco M. Goycoolea
- School of Food Science and Nutrition; University of Leeds; LS2 9JT Leeds UK
- Institut für Biologie und Biotechnologie der Pflanzen; Westfälische Wilhelms-Universität Münster; Schlossgarten 3 48149 Münster Germany
| | - Bianca Menchicchi
- Department of Medicine 1; University of Erlangen-Nueremberg; Hartmanstrasse 14 91052 Erlangen Germany
- Nanotechnology Group; Department of Plant Biology and Biotechnology; University of Münster; Schlossgarten 3 48149 Münster Germany
| | | | - Francesca Saporito
- Department of Drug Sciences; University of Pavia; Via Taramelli, 12 27100 Pavia Italy
| | - Seunghwan Lee
- Department of Mechanical Engineering; Technical University of Denmark; Produktionstorvet 2800 Kgs Lyngby Copenhagen Denmark
| | - Karen Stephansen
- National Food Institute; Technical University of Denmark; Søltofts Plads, 2800 Kgs Lyngby Copenhagen Denmark
| | - Ioannis S. Chronakis
- National Food Institute; Technical University of Denmark; Søltofts Plads, 2800 Kgs Lyngby Copenhagen Denmark
| | - Marianne Hiorth
- School of Pharmacy; University of Oslo; Postboks 1068 Blindern 0316 OSLO Norway
| | - Malgorzata Adamczak
- School of Pharmacy; University of Oslo; Postboks 1068 Blindern 0316 OSLO Norway
| | - Max Waldner
- Medizinische Klinik 1; Ulmenweg 18 91054 Erlangen Germany
| | - Hanne Mørck Nielsen
- Department of Pharmacy; University of Copenhagen; Universitetsparken 2 2100 Copenhagen Denmark
| | - Luciano Marcelloni
- S.I.I.T. S.r.l Pharmaceutical & Health Food Supplements; Via Canova 5/7-20090 Trezzano S/N Milan Italy
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22
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Thiolated polymers as mucoadhesive drug delivery systems. Eur J Pharm Sci 2017; 100:64-78. [PMID: 28087353 DOI: 10.1016/j.ejps.2017.01.008] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Revised: 01/04/2017] [Accepted: 01/09/2017] [Indexed: 11/22/2022]
Abstract
Mucoadhesion is the process of binding a material to the mucosal layer of the body. Utilising both natural and synthetic polymers, mucoadhesive drug delivery is a method of controlled drug release which allows for intimate contact between the polymer and a target tissue. It has the potential to increase bioavailability, decrease potential side effects and offer protection to more sensitive drugs such as proteins and peptide based drugs. The thiolation of polymers has, in the last number of years, come to the fore of mucoadhesive drug delivery, markedly improving mucoadhesion due to the introduction of free thiol groups onto the polymer backbone while also offering a more cohesive polymeric matrix for the slower and more controlled release of drug. This review explores the concept of mucoadhesion and the recent advances in both the polymers and the methods of thiolation used in the synthesis of mucoadhesive drug delivery devices.
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23
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Ping Y, Hu X, Yao Q, Hu Q, Amini S, Miserez A, Tang G. Engineering bioinspired bacteria-adhesive clay nanoparticles with a membrane-disruptive property for the treatment of Helicobacter pylori infection. NANOSCALE 2016; 8:16486-98. [PMID: 27605059 DOI: 10.1039/c6nr05551f] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/21/2023]
Abstract
We present a bioinspired design strategy to engineer bacteria-targeting and membrane-disruptive nanoparticles for the effective antibiotic therapy of Helicobacter pylori (H. pylori) infection. Antibacterial nanoparticles were self-assembled from highly exfoliated montmorillonite (eMMT) and cationic linear polyethyleneimine (lPEI) via electrostatic interactions. eMMT functions as a bioinspired 'sticky' building block for anchoring antibacterial nanoparticles onto the bacterial cell surface via bacteria-secreted extracellular polymeric substances (EPS), whereas membrane-disruptive lPEI is able to efficiently lyse the bacterial outer membrane to allow topical transmembrane delivery of antibiotics into the intracellular cytoplasm. As a result, eMMT-lPEI nanoparticles intercalated with the antibiotic metronidazole (MTZ) not only efficiently target bacteria via EPS-mediated adhesion and kill bacteria in vitro, but also can effectively remain in the stomach where H. pylori reside, thereby serving as an efficient drug carrier for the direct on-site release of MTZ into the bacterial cytoplasm. Importantly, MTZ-intercalated eMMT-lPEI nanoparticles were able to efficiently eradicate H. pylori in vivo and to significantly improve H. pylori-associated gastric ulcers and the inflammatory response in a mouse model, and also showed superior therapeutic efficacy as compared to standard triple therapy. Our findings reveal that bacterial adhesion plays a critical role in promoting efficient antimicrobial delivery and also represent an original bioinspired targeting strategy via specific EPS-mediated adsorption. The bacteria-adhesive eMMT-lPEI nanoparticles with membrane-disruptive ability may constitute a promising drug carrier system for the efficacious targeted delivery of antibiotics in the treatment of bacterial infections.
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Affiliation(s)
- Yuan Ping
- School of Materials Science and Engineering and Center for Biomimetic Sensor Science, Nanyang Technological University, Singapore 639798, Singapore.
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24
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Partenhauser A, Bernkop-Schnürch A. Mucoadhesive polymers in the treatment of dry X syndrome. Drug Discov Today 2016; 21:1051-62. [DOI: 10.1016/j.drudis.2016.02.013] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2015] [Revised: 02/05/2016] [Accepted: 02/23/2016] [Indexed: 11/29/2022]
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25
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Dey SK, De PK, De A, Ojha S, De R, Mukhopadhyay AK, Samanta A. Floating mucoadhesive alginate beads of amoxicillin trihydrate: A facile approach for H. pylori eradication. Int J Biol Macromol 2016; 89:622-31. [PMID: 27177460 DOI: 10.1016/j.ijbiomac.2016.05.027] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2016] [Revised: 05/03/2016] [Accepted: 05/08/2016] [Indexed: 12/13/2022]
Abstract
This study investigates the design of sunflower oil entrapped floating and mucoadhesive beads of amoxicillin trihydrate using sodium alginate and hydroxypropyl methylcellulose as matrix polymers and chitosan as coating polymer to localize the antibiotic at the stomach site against Helicobacter pylori. Beads prepared by ionotropic gellation technique were evaluated for different physicochemical, in-vitro and in-vivo properties. Beads of all batches were floated for >24h with a maximum lag time of 46.3±3.2s. Scanning electron microscopy revealed that the beads were spherical in shape with few oil filled channels distributed throughout the surfaces and small pocket structures inside the matrix confirming oil entrapment. Prepared beads showed good mucoadhesiveness of 75.7±3.0% to 85.0±5.5%. The drug release profile was best fitted to Higuchi model with non fickian driven mechanism. The optimized batch showed 100% Helicobacter pylori growth inhibition in 15h in in-vitro culture. Furthermore, X-ray study in rabbit stomach confirmed the gastric retention of optimized formulation. The results exhibited that formulated beads may be preferred to localize the antibiotic in the gastric region to allow more availability of antibiotic at gastric mucus layer acting on Helicobacter pylori, thereby improving the therapeutic efficacy.
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Affiliation(s)
- Sanjoy Kumar Dey
- Division of Microbiology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India
| | - Pintu Kumar De
- Department of Pharmaceutics, Dr. B. C. Roy College of Pharmacy and Allied Health Sciences, Bidhan Nagar, Durgapur 713206, India
| | - Arnab De
- Division of Microbiology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India
| | - Souvik Ojha
- Department of Pharmaceutics, Dr. B. C. Roy College of Pharmacy and Allied Health Sciences, Bidhan Nagar, Durgapur 713206, India
| | - Ronita De
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Beleghata, Kolkata 700010, India
| | - Asish Kumar Mukhopadhyay
- Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Beleghata, Kolkata 700010, India
| | - Amalesh Samanta
- Division of Microbiology, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
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26
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Verma A, Dubey J, Hegde RR, Rastogi V, Pandit JK. Helicobacter pylori: past, current and future treatment strategies with gastroretentive drug delivery systems. J Drug Target 2016; 24:897-915. [DOI: 10.3109/1061186x.2016.1171326] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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27
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Gajra B, Patel RR, Dalwadi C. Formulation, optimization and characterization of cationic polymeric nanoparticles of mast cell stabilizing agent using the Box–Behnken experimental design. Drug Dev Ind Pharm 2015; 42:747-57. [DOI: 10.3109/03639045.2015.1093496] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Balaram Gajra
- Department of Pharmaceutics and Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy (RPCP), Charotar University of Science and Technology (CHARUSAT), Changa, Gujarat, India,
| | - Ravi R. Patel
- Department of Pharmaceutics and Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy (RPCP), Charotar University of Science and Technology (CHARUSAT), Changa, Gujarat, India,
- Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India
| | - Chintan Dalwadi
- Department of Pharmaceutics and Pharmaceutical Technology, Ramanbhai Patel College of Pharmacy (RPCP), Charotar University of Science and Technology (CHARUSAT), Changa, Gujarat, India,
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28
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Kim SY, Choi DJ, Chung JW. Antibiotic treatment for Helicobacter pylori: Is the end coming? World J Gastrointest Pharmacol Ther 2015; 6:183-198. [PMID: 26558152 PMCID: PMC4635158 DOI: 10.4292/wjgpt.v6.i4.183] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 08/01/2015] [Accepted: 09/28/2015] [Indexed: 02/06/2023] Open
Abstract
Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori) has been associated with gastro-duodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Antibiotic resistance to clarithromycin and metronidazole is particularly problematic and several approaches have been proposed to overcome this issue, such as complementary probiotic therapy with Lactobacillus. Other studies have identified novel molecules with an anti-H. pylori effect, as well as tailored therapy and nanotechnology as viable alternative eradication strategies. This review discusses current antibiotic therapy for H. pylori infections, limitations of this type of therapy and predicts the availability of newly developed therapies for H. pylori eradication.
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29
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Fox CB, Kim J, Le LV, Nemeth CL, Chirra HD, Desai TA. Micro/nanofabricated platforms for oral drug delivery. J Control Release 2015; 219:431-444. [PMID: 26244713 DOI: 10.1016/j.jconrel.2015.07.033] [Citation(s) in RCA: 75] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2015] [Revised: 07/29/2015] [Accepted: 07/30/2015] [Indexed: 12/18/2022]
Abstract
The oral route of drug administration is most preferred due to its ease of use, low cost, and high patient compliance. However, the oral uptake of many small molecule drugs and biotherapeutics is limited by various physiological barriers, and, as a result, drugs suffer from issues with low solubility, low permeability, and degradation following oral administration. The flexibility of micro- and nanofabrication techniques has been used to create drug delivery platforms designed to address these barriers to oral drug uptake. Specifically, micro/nanofabricated devices have been designed with planar, asymmetric geometries to promote device adhesion and unidirectional drug release toward epithelial tissue, thereby prolonging drug exposure and increasing drug permeation. Furthermore, surface functionalization, nanotopography, responsive drug release, motion-based responses, and permeation enhancers have been incorporated into such platforms to further enhance drug uptake. This review will outline the application of micro/nanotechnology to specifically address the physiological barriers to oral drug delivery and highlight technologies that may be incorporated into these oral drug delivery systems to further enhance drug uptake.
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Affiliation(s)
- Cade B Fox
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158, USA
| | - Jean Kim
- UC Berkeley & UCSF Graduate Program in Bioengineering, UCSF Mission Bay Campus, San Francisco, CA 94158, USA
| | - Long V Le
- UC Berkeley & UCSF Graduate Program in Bioengineering, UCSF Mission Bay Campus, San Francisco, CA 94158, USA
| | - Cameron L Nemeth
- UC Berkeley & UCSF Graduate Program in Bioengineering, UCSF Mission Bay Campus, San Francisco, CA 94158, USA
| | - Hariharasudhan D Chirra
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158, USA
| | - Tejal A Desai
- Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158, USA; UC Berkeley & UCSF Graduate Program in Bioengineering, UCSF Mission Bay Campus, San Francisco, CA 94158, USA.
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30
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Harsha SN, Aldhubiab BE, Nair AB, Alhaider IA, Attimarad M, Venugopala KN, Srinivasan S, Gangadhar N, Asif AH. Nanoparticle formulation by Büchi B-90 Nano Spray Dryer for oral mucoadhesion. DRUG DESIGN DEVELOPMENT AND THERAPY 2015; 9:273-82. [PMID: 25670882 PMCID: PMC4315564 DOI: 10.2147/dddt.s66654] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Diabetes is considered one of the main threats to global public health in this era. It is increasing rapidly in every part of the world; the prevalence of the disease will grow to the point where 366 million people will be affected by 2030. The prevalence of diabetes mellitus (DM) in the Saudi population is high, and the majority of patients suffer from type 2 DM. Marketed oral antidiabetic drugs have indicated poor tolerability during chronic treatments, and this contributes to the moderately large proportion of type 2 DM patients that remain inadequately managed. Vildagliptin nanospheres were prepared with aminated gelatin using a spray-drying method; narrow particle-size distribution was seen at 445 nm. The angle of repose was found to be θ <33.5°. The nanospheres appeared to be spherical with a smooth surface. The drug content and percentage yield of the nanospheres were found to be 76.2%±4.6% and 83%±2%, respectively. The nanosphere-swell profile was found to be 165%±7%. The pure drug was 100% dissolved in 30 minutes, and the nanosphere formulation took 12 hours to dissolve (97.5%±2%), and followed a Korsmeyer-Peppas kinetic model with an R (2) of 0.9838. The wash-off test of nanospheres found that they exhibited an excellent mucoadhesive property at 86.7% for 8 hours. The stability-study data showed no changes in the physicochemical properties of the nanospheres, and suggested that the nanospheres be stored below room temperature. The amount of vildagliptin retained was 1.6% within 3 hours, and in comparison with the gelatin vildagliptin nanoparticles formulation, the percentage that was retained was much higher (98.2% in 12 hours).
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Affiliation(s)
- Sree N Harsha
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Bander E Aldhubiab
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Anroop B Nair
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Ibrahim Abdulrahman Alhaider
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Mahesh Attimarad
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | - Katharigatta N Venugopala
- Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
| | | | - Nagesh Gangadhar
- Department of Pharmaceutics, East Point College of Pharmacy, Bangalore, India
| | - Afzal Haq Asif
- Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia
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31
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Mucoadhesive polymers in the design of nano-drug delivery systems for administration by non-parenteral routes: A review. Prog Polym Sci 2014. [DOI: 10.1016/j.progpolymsci.2014.07.010] [Citation(s) in RCA: 333] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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32
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Lopes D, Nunes C, Martins MCL, Sarmento B, Reis S. Eradication of Helicobacter pylori: Past, present and future. J Control Release 2014; 189:169-86. [PMID: 24969353 DOI: 10.1016/j.jconrel.2014.06.020] [Citation(s) in RCA: 76] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Revised: 06/12/2014] [Accepted: 06/13/2014] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori is the major cause of chronic gastritis and peptic ulcers. Since the classification as a group 1 carcinogenic by International Agency for Research on Cancer, the importance of the complete H. pylori eradication has obtained a novel meaning. Hence, several studies have been made in order to deepen the knowledge in therapy strategies. However, the current therapy presents unsatisfactory eradication rates due to the lack of therapeutic compliance, antibiotic resistance, the degradation of antibiotics at gastric pH and their insufficient residence time in the stomach. Novel approaches have been made in order to overcome these limitations. The purpose of this review is to provide an overview about the current therapy and its limitations, while highlighting the possibility of using micro- and nanotechnology to develop gastric drug delivery systems, overcoming these difficulties in the future.
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Affiliation(s)
- Daniela Lopes
- REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
| | - Cláudia Nunes
- REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
| | - M Cristina L Martins
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal
| | - Bruno Sarmento
- INEB - Instituto de Engenharia Biomédica, Universidade do Porto, Porto, Portugal; IINFACTS - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Superior de Ciências da Saúde-Norte, Gandra-PRD, Portugal
| | - Salette Reis
- REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal.
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Hokugo A, Saito T, Li A, Sato K, Tabata Y, Jarrahy R. Stimulation of bone regeneration following the controlled release of water-insoluble oxysterol from biodegradable hydrogel. Biomaterials 2014; 35:5565-71. [PMID: 24731715 DOI: 10.1016/j.biomaterials.2014.03.018] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2014] [Accepted: 03/11/2014] [Indexed: 12/30/2022]
Abstract
Recently bone graft substitutes using bone morphogenetic proteins (BMPs) have been heralded as potential alternatives to traditional bone reconstruction procedures. BMP-based products, however, are associated with significant and potentially life-threatening side effects when used in the head and neck region and furthermore, are exorbitantly priced. Oxysterols, products of cholesterol oxidation, represent a class of molecules that are favorable alternatives or adjuncts to BMP therapy due to their low side effect profile and cost. In order to establish the optimal clinical utility of oxysterol, an optimal scaffold must be developed, one that allows the release of oxysterol in a sustained and efficient manner. In this study, we prepare a clinically applicable bone graft substitute engineered for the optimal release of oxysterol. We first solubilized oxysterol in water by making use of polymeric micelles using l-lactic acid oligomer (LAo) grafted gelatin. Then, the water-solubilized oxysterol was incorporated into a biodegradable hydrogel that was enzymatically degraded intracorporeally. In this manner, oxysterol could be released from the hydrogel in a degradation-driven manner. The water-solubilized oxysterol incorporated biodegradable hydrogel was implanted into rat calvarial defects and induced successful bone regeneration. The innovative significance of this study lies in the development of a bone graft substitute that couples the osteogenic activity of oxysterol with a scaffold designed for optimized oxysterol release kinetics, all of which lead to better repair of bone defects.
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Affiliation(s)
- Akishige Hokugo
- Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90025, USA
| | - Takashi Saito
- Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
| | - Andrew Li
- Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90025, USA
| | - Keisuke Sato
- Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
| | - Yasuhiko Tabata
- Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
| | - Reza Jarrahy
- Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90025, USA.
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34
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Chi JL, Li CC, Xia CQ, Li L, Ma Y, Li JH, Chen Z, Chen XL. Effect of (131)I gelatin microspheres on hepatocellular carcinoma in nude mice and its distribution after intratumoral injection. Radiat Res 2014; 181:416-24. [PMID: 24720750 DOI: 10.1667/rr13539.1] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
In this study, we investigated the effect of (131)I gelatin microspheres ((131)I-GMSs) on human hepatocellular carcinoma cells (HepG2) in nude mice (Balb/c) and the biodistribution of (131)I-GMSs after intratumoral injection. The treatment group and control group animals received intratumoral injections of 1 mCi (131)I-GMSs and GMSs unlabeled (131)I, respectively. The size of the implanted tumor was measured once a week for 8 weeks, and the survival time was calculated from the day of injection to 64 days post-injection. Another 35 animals received intratumoral injections of 0.2 mCi (131)I-GMSs and were subject to single-photon emission computed tomography (SPECT) on days 1, 8, 16, 24 and 32 post-injection. Samples of various organs were collected and used to calculate tissue concentrations on days 1, 4, 8, 16 and 24. Free thyroxine (FT4) in fetal bovine serum was tested to evaluate thyroid function. The tumors were collected for histological examination. (131)I-GMSs produced a pronounced reduction in HepG2 tumor volume, and the overall survival was 73.3% in the treatment group and only 13.3% in the control group (P < 0.001). Tissue radioactivity concentration measurements and SPECT demonstrated that the injected (131)I-GMSs mainly accumulated within the tumors. The concentration of FT4 was stable during the observation period. The microspheres could be observed by histological methods on day 32. (131)I-GMSs suppressed the growth of HepG2 in the nude mice and were retained in the tumor for a long period of time after injection. Direct intratumoral injection of (131)I-GMSs offers a promising modality for the treatment of hepatocellular carcinoma.
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Affiliation(s)
- Jun-Lin Chi
- a Department of Hepato-bilio-pancreatology Surgery, West China Hospital of Sichuan University, Chengdu 610041, China
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35
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Anirudhan TS, Rejeena SR. Poly(acrylic acid-co-acrylamide-co-2-acrylamido-2-methyl-1-propanesulfonic acid)-grafted nanocellulose/poly(vinyl alcohol) composite for thein vitrogastrointestinal release of amoxicillin. J Appl Polym Sci 2014. [DOI: 10.1002/app.40699] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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36
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The graft survival protection of subcutaneous allogeneic islets with hydrogel grafting and encapsulated by CTLA4Ig and IL1ra. Polym J 2013. [DOI: 10.1038/pj.2013.71] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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37
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Arora S, Budhiraja RD. Chitosan-alginate microcapsules of amoxicillin for gastric stability and mucoadhesion. J Adv Pharm Technol Res 2012; 3:68-74. [PMID: 22470897 PMCID: PMC3312731 DOI: 10.4103/2231-4040.93555] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
Amoxicillin-loaded microcapsules were prepared by ionotropic gelation of sodium alginate (ALG) with chitosan (CS) in presence of calcium chloride as gastroretentive delivery system. The effect of pH, concentration of ALG, CS and calcium chloride, and drug : ALG ratio were optimized in this study for minimizing the degradation of drug in acidic environment and increasing the loading efficacy and mucoadhesive efficiency of microcapsules. The optimum condition for prepared CS-ALG microcapsules was 2%w/v ALG, 0.75%w/v CS (pH5.0), and 1.0% w/v calcium chloride. The resulting microcapsules had drug entrapment efficiency of 84% and average size of 840 mm. CS concentration significantly influenced particle size and encapsulation efficiency of CS–ALG microcapsules (P<0.05). Decrease in the drug: ALG ratio resulted in an increased release of amoxicillin in acidic media. The relative decomposition of drug after encapsulation in CS-ALG microcapsules was decreased to 20.7%, 41.9%, and 83.3% in 2, 4, and 8 hours, respectively.
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Affiliation(s)
- Saahil Arora
- Department of Pharmaceutics, Nanomedicine Research Centre, I. S. F. College of Pharmacy, Moga (Punjab), India
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38
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Angadi SC, Manjeshwar LS, Aminabhavi TM. Novel composite blend microbeads of sodium alginate coated with chitosan for controlled release of amoxicillin. Int J Biol Macromol 2012; 51:45-55. [DOI: 10.1016/j.ijbiomac.2012.04.018] [Citation(s) in RCA: 79] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2012] [Revised: 04/11/2012] [Accepted: 04/17/2012] [Indexed: 11/26/2022]
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39
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Ko JA, Oh YS, Park HJ. Preparation and Characterization of Aminated Gelatin-Fucoidan Microparticles. ACTA ACUST UNITED AC 2012. [DOI: 10.9721/kjfst.2012.44.2.191] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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40
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Abstract
Many strategies have been proposed to explore the possibility of exploiting gastroretention for drug delivery. Such systems would be useful for local delivery, for drugs that are poorly soluble at higher pH or primarily absorbed from the proximal small intestine. Generally, the requirements of such strategies are that the vehicle maintains controlled drug release and exhibits prolonged residence time in the stomach. Despite widespread reporting of technologies, many have an inherent drawback of variability in transit times. Microparticulate systems, capable of distributing widely through the gastrointestinal tract, can potentially minimise this variation. While being retained in the stomach, the drug content is released slowly at a desired rate, resulting in reduced fluctuations in drug levels. This review summarises the promising role of microencapsulation in this field, exploring both floating and mucoadhesive microparticles and their application in the treatment of Helicobacter pylori, highlighting the clinical potential of eradication of this widespread infection.
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Affiliation(s)
- Adeola Adebisi
- School of Applied Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK
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41
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Arora S, Gupta S, Narang RK, Budhiraja RD. Amoxicillin loaded chitosan-alginate polyelectrolyte complex nanoparticles as mucopenetrating delivery system for h. Pylori. Sci Pharm 2011; 79:673-94. [PMID: 21886911 PMCID: PMC3163361 DOI: 10.3797/scipharm.1011-05] [Citation(s) in RCA: 72] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2010] [Accepted: 05/18/2011] [Indexed: 12/24/2022] Open
Abstract
The present study has been undertaken to apply the concept of nanoparticulate mucopenetrating drug delivery system for complete eradication of Helicobacter pylori (H. pylori), colonised deep into the gastric mucosal lining. Most of the existing drug delivery systems have failed on account of either improper mucoadhesion or mucopenetration and no dosage form with dual activity of adhesion and penetration has been designed till date for treating H. pylori induced disorders. In the present study, novel chitosan-alginate polyelectrolyte complex (CS-ALG PEC) nanoparticles of amoxicillin have been designed and optimized for various variables such as pH and mixing ratio of polymers, concentrations of polymers, drug and surfactant, using 33 Box-Behnken design. Various studies like particle size, surface charge, percent drug entrapment, in-vitro mucoadhesion and in-vivo mucopenetration of nanoparticles on rat models were conducted. The optimised FITC labelled CS-ALG PEC nanoparticles have shown comparative low in-vitro mucoadhesion with respect to plain chitosan nanoparticles, but excellent mucopenetration and localization as observed with increased fluorescence in gastric mucosa continuously over 6 hours, which clinically can help in eradication of H. pylori.
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Affiliation(s)
- Saahil Arora
- Nanomedicine Research Centre, Department of Pharmaceutics, I.S.F. College of Pharmacy, Moga-142001 (Punjab), India
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42
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Nagpal K, Singh SK, Mishra DN. Chitosan nanoparticles: a promising system in novel drug delivery. Chem Pharm Bull (Tokyo) 2011; 58:1423-30. [PMID: 21048331 DOI: 10.1248/cpb.58.1423] [Citation(s) in RCA: 365] [Impact Index Per Article: 26.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The ability of nanoparticles to manipulate the molecules and their structures has revolutionized the conventional drug delivery system. The chitosan nanoparticles, because of their biodegradability, biocompatibility, better stability, low toxicity, simple and mild preparation methods, offer a valuable tool to novel drug delivery systems in the present scenario. Besides ionotropic gelation method, other methods such as microemulsion method, emulsification solvent diffusion method, polyelectrolyte complex method, emulsification cross-linking method, complex coacervation method and solvent evaporation method are also in use. The chitosan nanoparticles have also been reported to have key applications in parentral drug delivery, per-oral administration of drugs, in non-viral gene delivery, in vaccine delivery, in ocular drug delivery, in electrodeposition, in brain targeting drug delivery, in stability improvement, in mucosal drug delivery in controlled drug delivery of drugs, in tissue engineering and in the effective delivery of insulin. The present review describes origin and properties of chitosan and its nanoparticles along with the different methods of its preparation and the various areas of novel drug delivery where it has got its application.
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Affiliation(s)
- Kalpana Nagpal
- Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar, India
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43
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Effect of microencapsulated precipitants of Lactobacillus casei ATCC 393 on Helicobacter pylori eradication. Process Biochem 2011. [DOI: 10.1016/j.procbio.2010.10.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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44
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Asane GS, Rao YM, Bhatt JH, Shaikh KS. Optimization, characterisation and pharmacokinetic studies of mucoadhesive oral multiple unit systems of ornidazole. Sci Pharm 2010; 79:181-96. [PMID: 21617782 PMCID: PMC3097506 DOI: 10.3797/scipharm.1003-03] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2010] [Accepted: 11/29/2010] [Indexed: 11/22/2022] Open
Abstract
The objective of the present study was to investigate the applicability of matrix type mucoadhesive oral multiple unit systems (MUS) for sustaining the release of ornidazole in the gastrointestinal tract (GIT). The MUS were prepared by ionotropic gelation method using chitosan and hydroxypropyl methyl cellulose K4M (HPMC K4M) according to 32 factorial designs and were evaluated in vitro and in vivo. The particle size length ranged from 0.78 to 1.30 mm and breadth from 0.76 to 1.30 mm, respectively. The entrapment efficiency was in range of 80 to 96%. The rapid wash-off test was observed faster at intestinal pH 6.8 as compared to acidic pH 1.2. The fluoroscopic study revealed the retention of MUS in GIT for more than 5 hours. The pharmacokinetic parameters Cmax, Tmax, mean residence time (MRT) and area under curve (AUC) of developed MUS were found to be improved significantly (p<0.05) when compared with marketed immediate release tablets each containing 500 mg of drug. This study demonstrates that the MUS could be a good alternative to immediate release tablets to deliver ornidazole and expected to be less irritant to gastric and intestinal mucosa.
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Affiliation(s)
- Govind S Asane
- Department of Pharmaceutics, Pravara Rural College of Pharmacy, Loni- 413736, India.
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45
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Pawar VK, Kansal S, Garg G, Awasthi R, Singodia D, Kulkarni GT. Gastroretentive dosage forms: a review with special emphasis on floating drug delivery systems. Drug Deliv 2010; 18:97-110. [PMID: 20958237 DOI: 10.3109/10717544.2010.520354] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
In the present era, gastroretentive dosage forms (GRDF) receive great attention because they can improve the performance of controlled release systems. An optimum GRDF system can be defined as a system which retains in the stomach for a sufficient time interval against all the physiological barriers, releases active moiety in a controlled manner, and finally is easily metabolized in the body. Physiological barriers like gastric motility and gastric retention time (GRT) act as obstacles in developing an efficient GRDF. Gastroretention can be achieved by developing different systems like high density systems, floating drug delivery systems (FDDS), mucoadhesive systems, expandable systems, superporous systems, and magnetic systems. All these systems have their own merits and demerits. This review focused on the various aspects useful in development of GRDF including the current trends and advancements.
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Affiliation(s)
- Vivek K Pawar
- Department of Pharmaceutical Technology, Meerut Institute of Engineering and Technology, NH- 58, Uttar Pradesh, 250002, India.
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46
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Sahasathian T, Praphairaksit N, Muangsin N. Mucoadhesive and floating chitosan-coated alginate beads for the controlled gastric release of amoxicillin. Arch Pharm Res 2010; 33:889-99. [PMID: 20607494 DOI: 10.1007/s12272-010-0612-8] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2009] [Revised: 01/10/2010] [Accepted: 02/04/2010] [Indexed: 10/19/2022]
Abstract
This work focused on the development of mucoadhesive and floating chitosan-coated alginate beads as a gastroretensive delivery vehicle for amoxicillin, towards the effective eradication of Helicobacter pylori, a major causative agent of peptic ulcers. Alginate was used as the core bead core polymer and chitosan as the mucoadhesive polymer coating. Amoxicillin-loaded alginate beads coated with 0.5% (w/v) chitosan (ALG/0.5%CHI) exhibited excellent floating ability, high encapsulation efficiency, high drug loading capacity, and a strong in vitro mucoadhesion to the gastric mucosal layer. In vitro, amoxicillin was released faster in simulated gastric fluid (pH 1.2, HCl) than in simulated intestinal fluid (phosphate buffer, pH 7.4). ALG/0.5%CHI could be prepared with a > 90% drug encapsulation efficiency and exhibited more than 90% muco-adhesiveness, 100% floating ability, and achieved sustained release of amoxicillin for over six hours in SGF.
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Affiliation(s)
- Teerawat Sahasathian
- Program of Petrochemistry and Polymer Science, Chulalongkorn University, Bangkok, Thailand
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47
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Lin WJ, Kang WW. Comparison of chitosan and gelatin coated microparticles: Prepared by hot-melt method. J Microencapsul 2010. [DOI: 10.3109/02652040309178059] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- W.-J. Lin
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan
| | - W.-W. Kang
- School of Pharmacy, College of Medicine, National Taiwan University, Taipei 100, Taiwan
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48
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Park J, Kim D. Effect of polymer solution concentration on the swelling and mechanical properties of glycol chitosan superporous hydrogels. J Appl Polym Sci 2010. [DOI: 10.1002/app.30632] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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49
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Narkar M, Sher P, Pawar A. Stomach-specific controlled release gellan beads of acid-soluble drug prepared by ionotropic gelation method. AAPS PharmSciTech 2010; 11:267-77. [PMID: 20180053 DOI: 10.1208/s12249-010-9384-1] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2009] [Accepted: 01/23/2010] [Indexed: 01/05/2023] Open
Abstract
The purpose of the present work was the development and evaluation of stomach-specific controlled release mucoadhesive drug delivery system prepared by ionotropic gelation of gellan beads, containing acid-soluble drug amoxicillin trihydrate, using 3(2) factorial design with concentration of gellan gum and quantity of drug as variables. The study showed that beads prepared in alkaline cross-linking medium have higher entrapment efficiency than the acidic cross-linking medium. The entrapment efficiency was in the range of 32% to 46% w/w in acidic medium, which increased up to 60% to 90% w/w in alkaline medium. Batches with lowest, medium, and highest drug entrapment were subjected to chitosan coating to form a polyelectrolyte complex film. As polymer concentration increases, entrapment efficiency and particle size increases. Scanning electron microscopy revealed spherical but rough surface due to leaching of drug in acidic cross-linking solution, dense spherical structure in alkaline cross-linking solution, and rough surface of chitosan-coated beads with minor wrinkles. The in vitro drug release up to 7 h in a controlled manner following the Peppas model (r = 0.9998). In vitro and in vivo mucoadhesivity study showed that beads have good mucoadhesivity and more than 85% beads remained adhered to stomach mucosa of albino rat even after 7 h. In vitro growth inhibition study showed complete eradication of Helicobacter pylori. These results indicate that stomach-specific controlled release mucoadhesive system of amoxicillin gellan beads may be useful in H. pylori treatment.
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50
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Morimoto K, Chono S, Kosai T, Seki T, Tabata Y. Design of novel injectable cationic microspheres based on aminated gelatin for prolonged insulin action. J Pharm Pharmacol 2010; 57:839-44. [PMID: 15969942 DOI: 10.1211/0022357056415] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Abstract
The aim of this study was to prepare two types of injectable cationized microspheres based on a native gelatin (NGMS) and aminated gelatin with ethylenediamine (CGMS) to prolong the action of insulin. Release of rhodamin B isothiocyanate insulin from CGMS was compared with that from NGMS under in-vitro and in-vivo conditions. Lower release of insulin from CGMS compared with that from NGMS was caused by the suppression of initial release. The disappearance of 125I-insulin from the injection site after intramuscular administration by NGMS and CGMS had a biphasic profile in mice. Almost all the 125I-insulin had disappeared from the injection site one day after administration by NGMS. The remaining insulin at the injection site after administration by CGMS was prolonged, with approximately 59% remaining after one day and 16% after 14 days. The disappearance of CGMS from the injection site was lower than that of NGMS. However, the difference in these disappearance rates was not great compared with those of 125I-insulin from the injection site by NGMS and CGMS. The time course of disappearance of 125I-CGMS from the injection site was similar to that of 125I-insulin by CGMS. The initial hypoglycaemic effect was observed 1h after administration of insulin by NGMS, thereafter its effect rapidly disappeared. The hypoglycaemic effect was observed 2–4h after administration by CGMS and continued to be exhibited for 7 days. The prolonged hypoglycaemic action by CGMS depended on the time profiles of the disappearance of insulin from muscular tissues, which occurs due to the enzymatic degradation of CGMS.
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Affiliation(s)
- Kazuhiro Morimoto
- Hokkaido Pharmaceutical University, School of Pharmacy, Otaru, Hokkaido 047-0264, Japan.
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