|
1
|
Kiilerich KF, Andresen T, Darbani B, Gregersen LHK, Liljensøe A, Bennike TB, Holm R, Moeller JB, Andersen V. Advancing Inflammatory Bowel Disease Treatment by Targeting the Innate Immune System and Precision Drug Delivery. Int J Mol Sci 2025; 26:575. [PMID: 39859291 PMCID: PMC11765494 DOI: 10.3390/ijms26020575] [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: 11/13/2024] [Revised: 01/04/2025] [Accepted: 01/09/2025] [Indexed: 01/27/2025] Open
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Current immune-modulating therapies are insufficient for 30-50% of patients or cause significant side effects, emphasizing the need for new treatments. Targeting the innate immune system and enhancing drug delivery to inflamed gut regions are promising strategies. Neutrophils play a central role in IBD by releasing reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) -DNA-based structures with cytotoxic proteins-that contribute to mucosal damage and inflammation. Recent studies linking ROS production, DNA repair, and NET formation have identified NETs as potential therapeutic targets, with preclinical models showing positive outcomes from NET inhibition. Innovative oral drug delivery systems designed to target gut inflammation directly-without systemic absorption-could improve treatment precision and reduce side effects. Advanced formulations utilize properties such as particle size, surface modifications, and ROS-triggered release to selectively target the distal ileum and colon. A dual strategy that combines a deeper understanding of IBD pathophysiology to identify inflammation-related therapeutic targets with advanced drug delivery systems may offer significant promise. For instance, pairing NET inhibition with ROS-responsive nanocarriers could enhance treatment efficacy, though further research is needed. This synergistic approach has the potential to greatly improve outcomes for IBD patients.
Collapse
Affiliation(s)
- Kat F. Kiilerich
- Department of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark; (K.F.K.); (J.B.M.)
| | - Trine Andresen
- Department of Health Science and Technology, The Faculty of Medicine, Aalborg University, 9220 Aalborg Ø, Denmark; (T.A.); (T.B.B.)
| | - Behrooz Darbani
- Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark; (B.D.); (L.H.K.G.); (A.L.)
| | - Laura H. K. Gregersen
- Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark; (B.D.); (L.H.K.G.); (A.L.)
- Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark
| | - Anette Liljensøe
- Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark; (B.D.); (L.H.K.G.); (A.L.)
| | - Tue B. Bennike
- Department of Health Science and Technology, The Faculty of Medicine, Aalborg University, 9220 Aalborg Ø, Denmark; (T.A.); (T.B.B.)
- Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark; (B.D.); (L.H.K.G.); (A.L.)
| | - René Holm
- Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5000 Odense, Denmark;
| | - Jesper B. Moeller
- Department of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark; (K.F.K.); (J.B.M.)
- Danish Institute for Advanced Study, University of Southern Denmark, 5000 Odense, Denmark
| | - Vibeke Andersen
- Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark; (B.D.); (L.H.K.G.); (A.L.)
- Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark
| |
Collapse
|
|
2
|
Jiang HY, Shao B, Wang HD, Zhao WQ, Ren SH, Xu YN, Liu T, Sun CL, Xiao YY, Li YC, Chen Q, Zhao PY, Yang GM, Liu X, Ren YF, Wang H. Analysis of nanomedicine applications for inflammatory bowel disease: structural and temporal dynamics, research hotspots, and emerging trends. Front Pharmacol 2025; 15:1523052. [PMID: 39845796 PMCID: PMC11750799 DOI: 10.3389/fphar.2024.1523052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 12/24/2024] [Indexed: 01/24/2025] Open
Abstract
Background The application of nanomedicine in inflammatory bowel disease (IBD) has gained significant attention in the recent years. As the field rapidly evolves, analyzing research trends and identifying research hotpots are essential for guiding future advancements, and a comprehensive bibliometric can provide valuable insights. Methods The current research focused on publications from 2001 to 2024, and was sourced from the Web of Science Core Collection (WoSCC). CiteSpace and VOSviewer were employed to visualize authors, institutions, countries, co-cited references, and keywords, thereby mapping the intellectual structure and identifying emerging trends in the field. Results The analysis covered 1,518 literature across 447 journals, authored by 9,334 researchers from 5,459 institutions and 287 countries/regions. The global publication numbers exhibited an upward trend, particularly in the last decade, with China leading as the top publishing country and the Chinese Academy of Sciences emerging as the foremost institution. Dr. Xiao Bo is the prominent figure in advanced drug delivery systems. This interdisciplinary field, which spans materials science, pharmacy, and medicine, has seen influential publications mainly concentrated on targeted nanoparticles treatment for IBD. Keyword analysis revealed that current research hotspots include drug delivery, immune cell regulation, antioxidant damage, intestinal microbiota homeostasis, and nanovesicles. Conclusion This study offers a comprehensive overview of global research landscape, emphasizing the rapid growth and increasing complexity of this field. It identifies key research hotspots and trends, including efforts to enhance the precision, efficacy, and safety of nanomedicine applications. Emerging directions are highlighted as crucial for further progress in this evolving area.
Collapse
Affiliation(s)
- Hong-Yu Jiang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Bo Shao
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Hong-Da Wang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Wen-Qi Zhao
- Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin, China
| | - Shao-Hua Ren
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
- Department of General Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
| | - Yi-Ni Xu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Tong Liu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Cheng-Lu Sun
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Yi-Yi Xiao
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Yi-Cheng Li
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Qiang Chen
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Peng-Yu Zhao
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Guang-Mei Yang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Xu Liu
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Yu-Fan Ren
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
| | - Hao Wang
- Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin General Surgery Institute, Tianjin Medical University General Hospital, Tianjin, China
- Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin, China
| |
Collapse
|
|
3
|
Li S, Wu T, Wu J, Chen W, Zhang D. Recognizing the biological barriers and pathophysiological characteristics of the gastrointestinal tract for the design and application of nanotherapeutics. Drug Deliv 2024; 31:2415580. [PMID: 39404464 PMCID: PMC11485891 DOI: 10.1080/10717544.2024.2415580] [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: 05/07/2024] [Revised: 10/04/2024] [Accepted: 10/07/2024] [Indexed: 10/19/2024] Open
Abstract
The gastrointestinal tract (GIT) is an important and complex system by which humans to digest food and absorb nutrients. The GIT is vulnerable to diseases, which may led to discomfort or even death in humans. Therapeutics for GIT disease treatment face multiple biological barriers, which significantly decrease the efficacy of therapeutics. Recognizing the biological barriers and pathophysiological characteristics of GIT may be helpful to design innovative therapeutics. Nanotherapeutics, which have special targeting and controlled therapeutic release profiles, have been widely used for the treatment of GIT diseases. Herein, we provide a comprehensive review of the biological barrier and pathophysiological characteristics of GIT, which may aid in the design of promising nanotherapeutics for GIT disease treatment. Furthermore, several typical diseases of the upper and lower digestive tracts, such as Helicobacter pylori infection and inflammatory bowel disease, were selected to investigate the application of nanotherapeutics for GIT disease treatment.
Collapse
Affiliation(s)
- Shan Li
- Department of Chemistry, College of Basic Medicine, Army Medical University (Third Military Medical University), Chongqing, China
- Department of Gastroenterology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
- Army 953 Hospital, Shigatse Branch of Xinqiao Hospital, Army Medical University (Third Military Medical University), Shigatse, Tibet Autonomous Region, China
| | - Tianyu Wu
- Department of Gastroenterology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Jingfeng Wu
- Department of Gastroenterology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Wensheng Chen
- Department of Gastroenterology, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China
| | - Dinglin Zhang
- Department of Chemistry, College of Basic Medicine, Army Medical University (Third Military Medical University), Chongqing, China
| |
Collapse
|
|
4
|
Liang W, Zhang W, Tian J, Zhang X, Lv X, Qu A, Chen J, Wu Z. Advances in carbohydrate-based nanoparticles for targeted therapy of inflammatory bowel diseases: A review. Int J Biol Macromol 2024; 281:136392. [PMID: 39423983 DOI: 10.1016/j.ijbiomac.2024.136392] [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: 05/18/2024] [Revised: 09/13/2024] [Accepted: 10/05/2024] [Indexed: 10/21/2024]
Abstract
The incidence of inflammatory bowel disease (IBD), a chronic gastrointestinal disorder, is rapidly increasing worldwide. Unfortunately, the current therapies for IBD are often hindered by premature drug release and undesirable side effects. With the advancement of nanotechnology, the innovative targeted nanotherapeutics are explored to ensure the accurate delivery of drugs to specific sites in the colon, thereby reducing side effects and improving the efficacy of oral administration. The emphasis of this review is to summarize the potential pathogenesis of IBD and highlight recent breakthroughs in carbohydrate-based nanoparticles for IBD treatment, including their construction, release mechanism, potential targeting ability, and their therapeutic efficacy. Specifically, we summarize the latest knowledge regarding environmental-responsive nano-systems and active targeted nanoparticles. The environmental-responsive drug delivery systems crafted with carbohydrates or other biological macromolecules like chitosan and sodium alginate, exhibit a remarkable capacity to enhance the accumulation of therapeutic drugs in the inflamed regions of the digestive tract. Active targeting strategies improve the specificity and accuracy of oral drug delivery to the colon by modifying carbohydrates such as hyaluronic acid and mannose onto nanocarriers. Finally, we discuss the challenges and provide insight into the future perspectives of colon-targeted delivery systems for IBD treatment.
Collapse
Affiliation(s)
- Wenjing Liang
- Tianjin Key Laboratory of Food Science and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China
| | - Wen Zhang
- Tianjin Key Laboratory of Food Science and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China; Key Laboratory of Low Carbon Cold Chain for Agricultural Products, Ministry of Agriculture and Rural Affairs, China.
| | - Jiayi Tian
- Tianjin Key Laboratory of Food Science and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China
| | - Xinping Zhang
- Tianjin Key Laboratory of Food Science and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China
| | - Xinyi Lv
- Tianjin Key Laboratory of Food Science and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China
| | - Ao Qu
- Tianjin Key Laboratory of Food Science and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China
| | - Jinyu Chen
- Tianjin Key Laboratory of Food Science and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China; Key Laboratory of Low Carbon Cold Chain for Agricultural Products, Ministry of Agriculture and Rural Affairs, China
| | - Zijian Wu
- Tianjin Key Laboratory of Food Science and Biotechnology, School of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China; Key Laboratory of Low Carbon Cold Chain for Agricultural Products, Ministry of Agriculture and Rural Affairs, China.
| |
Collapse
|
|
5
|
Yang M, Zhu Y, Wei X, Feng J, He Y, Jiang J, Zhou Q, Zhang M, Zhang G, Ma W. Oral bomb effect nanotherapeutics alleviate ulcerative colitis through coordinated anti-inflammatory and pro-resolving strategies. Biomater Sci 2024; 12:5386-5403. [PMID: 39264298 DOI: 10.1039/d4bm00843j] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/13/2024]
Abstract
Background: Ulcerative colitis (UC) is a debilitating chronic inflammatory bowel disease, and current treatments primarily focus on suppressing inflammation with limited efficacy. However, the resolution of inflammation also plays a crucial role in UC prognosis. Combining anti-inflammatory and pro-inflammatory resolution interventions may be a promising approach for treating UC. Materials and methods: The nano-bomb nanoparticles were validated for their ability to load CD98 siRNA (siCD98) and Annexin A1-mimetic peptides (Ac2-26 peptides), as well as release CO2 upon lysosomal escape. Surface modification with hyaluronic acid (HA) was assessed for its capability to target inflammatory tissues and cells. Biocompatibility and biosafety were evaluated through in vitro and in vivo studies. The anti-inflammatory and pro-resolving effects of siCD98@NPs and Ac2-26@NPs, both individually and in combination, were evaluated by measuring ROS production, pro-inflammatory cytokine expression, CD98 gene expression, and macrophage polarization. Results: These nanoparticles could efficiently load siCD98 and Ac2-26 peptides and release CO2 under acidic pH in the endo/lysosome to deliver drugs to the cytoplasm. HA could effectively target the inflammatory tissue and cells, showing good biocompatibility and biosafety both in vitro and in vivo. siCD98@NPs and Ac2-26@NPs showed anti-inflammatory effects by eliminating the over-production of ROS and down-regulating the expression of pro-inflammatory cytokines (TNF-α and IL-1β) and the CD98 gene; meanwhile, it showed pro-resolving function by inhibiting M0 to pro-inflammatory M1 macrophage conversion, with a more pronounced effect when combined with siCD98 and Ac2-26. The oral administration of chitosan-alginate hydrogel-encapsulated nanoparticles in UC model mice effectively alleviated inflammatory symptoms, reduced the expression of pro-inflammatory cytokines (TNF-α and IL-1β) and the CD98 gene, restored intestinal barrier function, and promoted M1 to M2 polarization, with a more pronounced effect when combined. Conclusion: By combining anti-inflammatory and pro-resolution interventions, these nanoparticles offer a novel therapeutic approach. This study offered a new approach for combination therapy of UC.
Collapse
Affiliation(s)
- Mei Yang
- Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
- Key Laboratory of Enhanced Recovery After Surgery of Integrated Chinese and Western Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yuanyuan Zhu
- School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Xiaodan Wei
- Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
- Key Laboratory of Enhanced Recovery After Surgery of Integrated Chinese and Western Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Jinteng Feng
- Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
- Key Laboratory of Enhanced Recovery After Surgery of Integrated Chinese and Western Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yingli He
- Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Jue Jiang
- Department of Medical Ultrasound, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
| | - Qi Zhou
- Department of Medical Ultrasound, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
| | - Mingzhen Zhang
- School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Guangjian Zhang
- Department of Thoracic Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
- Key Laboratory of Enhanced Recovery After Surgery of Integrated Chinese and Western Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Wenqi Ma
- Department of Medical Ultrasound, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
| |
Collapse
|
|
6
|
Wang A, Liu Y, Xiong W, Li W, Li J, Yang Z, Zou Z, Luo Y, Chen Z, Li H, Vong CT, Zou L. Targeting Inflammatory Lesions Facilitated by Galactosylation Modified Delivery System Eudragit/Gal-PLGA@Honokiol for the treatment of Ulcerative Colitis. J Pharm Sci 2024; 113:2744-2755. [PMID: 38901529 DOI: 10.1016/j.xphs.2024.06.010] [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: 01/30/2024] [Revised: 06/10/2024] [Accepted: 06/11/2024] [Indexed: 06/22/2024]
Abstract
Honokiol (HNK) is one of the bioactive ingredients from the well-known Chinese herbal medicine Magnolia officinalis, and its research interests is rising for its extensive pharmacological activities, including novel therapeutic effect on ulcerative colitis (UC). However, further application of HNK is largely limited by its unique physicochemical properties, such as poor water solubility, low bioavailability, as well as unsatisfied targeting efficacy for inflammatory lesions. In this study, we constructed galactosylation modified PLGA nanoparticles delivery system for efficient target delivery of HNK to the colitic lesions, which could lay a research foundation for the deep development of HNK for the treatment of UC. D-galactose was grafted by chemical coupling reactions with PLGA to prepare Gal-PLGA, which was used as a carrier for HNK (Gal-PLGA@HNK nanoparticles (NPs)). To improve the colon targeting efficiency by oral administration of the NPs, Eudragit S100 was used for wrapping on the surface of Gal-PLGA@HNK NPs (E/Gal-PLGA@HNK NPs). Our results showed that the encapsulation efficiency and drug loading capacity of E/Gal-PLGA@HNK NPs were 90.72 ± 0.54% and 8.41 ± 0.02%, respectively. Its average particle size was 242.24 ± 8.42 nm, with a PDI value of 0.135 ± 0.06 and zeta-potential of -16.83 ± 1.89 mV. The release rate of HNK from E/Gal-PLGA@HNK NPs was significantly decreased when compared with that of free HNK in simulated gastric and intestinal fluids, which displayed a slow-releasing property. It was also found that the cellular uptake of E/Gal-PLGA@HNK NPs was significantly increased when compared with that of free HNK in RAW264.7 cells, which was facilitated by D-galactose grafting on the PLGA carrier. Additionally, our results showed that E/Gal-PLGA@HNK NPs significantly improved colonic atrophy, body weight loss, as well as reducing disease activity index (DAI) score and pro-inflammatory cytokine levels in UC mice induced by DSS. Besides, the retention time of E/Gal-PLGA@HNK NPs in the colon was significantly increased when compared with that of other preparations, suggesting that these NPs could prolong the interaction between HNK and the injured colon. Taken together, the efficiency for target delivery of HNK to the inflammatory lesions was significantly improved by galactosylation modification on the PLGA carrier, which provided great benefits for the alleviation of colonic inflammation and injury in mice.
Collapse
Affiliation(s)
- Anqi Wang
- School of Food and Bioengineering, Institute for advanced study, Chengdu University, Chengdu 610106, China; Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China
| | - Yuanyuan Liu
- Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China
| | - Wugui Xiong
- School of Food and Bioengineering, Institute for advanced study, Chengdu University, Chengdu 610106, China
| | - Wei Li
- School of Preclinical Medicine, Chengdu University, Chengdu 610106, China
| | - Jin Li
- Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China
| | - Zhiqiang Yang
- Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China
| | - Zhongtao Zou
- Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China
| | - Yinjia Luo
- Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China
| | - Zhoujiang Chen
- School of Food and Bioengineering, Institute for advanced study, Chengdu University, Chengdu 610106, China
| | - Hanmei Li
- School of Food and Bioengineering, Institute for advanced study, Chengdu University, Chengdu 610106, China
| | - Chi Teng Vong
- Macau Centre for Research and Development in Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China
| | - Liang Zou
- School of Food and Bioengineering, Institute for advanced study, Chengdu University, Chengdu 610106, China; Antibiotics Research and Re-Evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, Chengdu University, Chengdu 610052, China.
| |
Collapse
|
|
7
|
Zheng B, Wang L, Yi Y, Yin J, Liang A. Design strategies, advances and future perspectives of colon-targeted delivery systems for the treatment of inflammatory bowel disease. Asian J Pharm Sci 2024; 19:100943. [PMID: 39246510 PMCID: PMC11375318 DOI: 10.1016/j.ajps.2024.100943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 05/02/2024] [Accepted: 05/21/2024] [Indexed: 09/10/2024] Open
Abstract
Inflammatory bowel diseases (IBD) significantly contribute to high mortality globally and negatively affect patients' qualifications of life. The gastrointestinal tract has unique anatomical characteristics and physiological environment limitations. Moreover, certain natural or synthetic anti-inflammatory drugs are associated with poor targeting, low drug accumulation at the lesion site, and other side effects, hindering them from exerting their therapeutic effects. Colon-targeted drug delivery systems represent attractive alternatives as novel carriers for IBD treatment. This review mainly discusses the treatment status of IBD, obstacles to drug delivery, design strategies of colon-targeted delivery systems, and perspectives on the existing complementary therapies. Moreover, based on recent reports, we summarized the therapeutic mechanism of colon-targeted drug delivery. Finally, we addressed the challenges and future directions to facilitate the exploitation of advanced nanomedicine for IBD therapy.
Collapse
Affiliation(s)
- Baoxin Zheng
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Liping Wang
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Yan Yi
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| | - Jun Yin
- School of Traditional Chinese Material, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Aihua Liang
- Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
| |
Collapse
|
|
8
|
Wang Y, Li Z, Bao Y, Cui H, Li J, Song B, Wang M, Li H, Cui X, Chen Y, Chen W, Yang S, Yang Y, Jin Z, Si X, Li B. Colon-targeted delivery of polyphenols: construction principles, targeting mechanisms and evaluation methods. Crit Rev Food Sci Nutr 2023; 65:64-86. [PMID: 37823723 DOI: 10.1080/10408398.2023.2266842] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/13/2023]
Abstract
Polyphenols have received considerable attention for their promotive effects on colonic health. However, polyphenols are mostly sensitive to harsh gastrointestinal environments, thus, must be protected. It is necessary to design and develop a colon-targeted delivery system to improve the stability, colon-targeting and bioavailability of polyphenols. This paper mainly introduces research on colon-targeted controlled release of polyphenols. The physiological features affecting the dissolution, release and absorption of polyphenol-loaded delivery systems in the colon are first discussed. Simultaneously, the types of colon-targeted carriers with different release mechanisms are described, and colon-targeting assessment models that have been studied so far and their advantages and limitations are summarized. Based on the current research on polyphenols colon-targeting, outlook and reflections are proposed, with the goal of inspiring strategic development of new colon-targeted therapeutics to ensure that the polyphenols reach the colon with complete bioactivity.
Collapse
Affiliation(s)
- Yidi Wang
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, China
| | - Zhiying Li
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, China
| | - Yiwen Bao
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, China
| | - Huijun Cui
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, China
| | - Jiaxin Li
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, China
| | - Baoge Song
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, China
| | - Mengzhu Wang
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, China
| | - Haikun Li
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, China
| | - Xingyue Cui
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, China
| | - Yi Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, Jiangxi, China
| | - Wei Chen
- Faculty of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, China
| | - Shufang Yang
- Zhejiang Lanmei Technology Co., Ltd, Zhu-ji City, Zhejiang Province, China
| | - Yiyun Yang
- Zhejiang Lanmei Technology Co., Ltd, Zhu-ji City, Zhejiang Province, China
| | - Zhufeng Jin
- Zhejiang Lanmei Technology Co., Ltd, Zhu-ji City, Zhejiang Province, China
| | - Xu Si
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, China
| | - Bin Li
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, China
| |
Collapse
|
|
9
|
Chintapula U, Chikate T, Sahoo D, Kieu A, Guerrero Rodriguez ID, Nguyen KT, Trott D. Immunomodulation in age-related disorders and nanotechnology interventions. WILEY INTERDISCIPLINARY REVIEWS. NANOMEDICINE AND NANOBIOTECHNOLOGY 2023; 15:e1840. [PMID: 35950266 PMCID: PMC9840662 DOI: 10.1002/wnan.1840] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 05/19/2022] [Accepted: 06/01/2022] [Indexed: 01/31/2023]
Abstract
Recently, the aging population has increased exponentially around the globe bringing more challenges to improve quality of life in those populations while reducing the economic burden on healthcare systems. Aging is associated with changes in the immune system culminating in detrimental effects such as immune dysfunction, immunosenescence, and chronic inflammation. Age-related decline of immune functions is associated with various pathologies including cardiovascular, autoimmune, neurodegenerative, and infectious diseases to name a few. Conventional treatment addresses the onset of age-related diseases by early detection of risk factors, administration of vaccines as preventive care, immunomodulatory treatment, and other dietary supplements. However, these approaches often come with systemic side-effects, low bioavailability of therapeutic agents, and poor outcomes seen in the elderly. Recent innovations in nanotechnology have led to the development of novel biomaterials/nanomaterials, which explore targeted drug delivery and immunomodulatory interactions in vivo. Current nanotechnology-based immunomodulatory approaches that have the potential to be used as therapeutic interventions for some prominent age-related diseases are discussed here. Finally, we explore challenges and future aspects of nanotechnology in the treatments of age-related disorders to improve quality of life in the elderly. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Therapeutic Approaches and Drug Discovery > Emerging Technologies.
Collapse
Affiliation(s)
- Uday Chintapula
- Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, USA
- Joint Bioengineering Program, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Tanmayee Chikate
- Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, USA
| | - Deepsundar Sahoo
- Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, USA
| | - Amie Kieu
- Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, USA
| | | | - Kytai T. Nguyen
- Department of Bioengineering, University of Texas at Arlington, Arlington, Texas, USA
- Joint Bioengineering Program, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| | - Daniel Trott
- Department of Kinesiology, University of Texas at Arlington, Arlington, Texas, USA
| |
Collapse
|
|
10
|
Mohajeri S, Moayedi S, Mohajeri S, Yadegar A, Haririan I. Targeting pathophysiological changes using biomaterials-based drug delivery systems: A key to managing inflammatory bowel disease. Front Pharmacol 2022; 13:1045575. [PMID: 36438794 PMCID: PMC9685402 DOI: 10.3389/fphar.2022.1045575] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 10/27/2022] [Indexed: 08/04/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a gastrointestinal disorder, affecting about several million people worldwide. Current treatments fail to adequately control some clinical symptoms in IBD patients, which can adversely impact the patient's quality of life. Hence, the development of new treatments for IBD is needed. Due to their unique properties such as biocompatibility and sustained release of a drug, biomaterials-based drug delivery systems can be regarded as promising candidates for IBD treatment. It is noteworthy that considering the pathophysiological changes occurred in the gastrointestinal tract of IBD patients, especially changes in pH, surface charge, the concentration of reactive oxygen species, and the expression of some biomolecules at the inflamed colon, can help in the rational design of biomaterials-based drug delivery systems for efficient management of IBD. Here, we discuss about targeting these pathophysiological changes using biomaterials-based drug delivery systems, which can provide important clues to establish a strategic roadmap for future studies.
Collapse
Affiliation(s)
- Sahar Mohajeri
- Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeed Moayedi
- Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Shabnam Mohajeri
- Faculty of Food Science and Technology, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ismaeil Haririan
- Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
11
|
Li DF, Yang MF, Xu HM, Zhu MZ, Zhang Y, Tian CM, Nie YQ, Wang JY, Liang YJ, Yao J, Wang LS. Nanoparticles for oral delivery: targeted therapy for inflammatory bowel disease. J Mater Chem B 2022; 10:5853-5872. [PMID: 35876136 DOI: 10.1039/d2tb01190e] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
As a group of chronic and idiopathic gastrointestinal (GI) disorders, inflammatory bowel disease (IBD) is characterized by recurrent intestinal mucosal inflammation. Oral administration is critical for the treatment of IBD. Unfortunately, it is difficult to target the bowel located in the GI tract due to multiple physical barriers. The unique physicochemical properties of nanoparticle-based drug delivery systems (DDSs) and their enhanced permeability and retention effects in the inflamed bowel, render nanomedicines to be used to implement precise drug delivery at diseased sites in IBD therapy. In this review, we described the pathophysiological features of IBD, and designed strategies to exploit these features for intestinal targeting. In addition, we introduced the types of currently developed nano-targeted carriers, including synthetic nanoparticle-based and emerging naturally derived nanoparticles (e.g., extracellular vesicles and plant-derived nanoparticles). Moreover, recent developments in targeted oral nanoparticles for IBD therapy were also highlighted. Finally, we presented challenges associated with nanotechnology and potential directions for future IBD treatment.
Collapse
Affiliation(s)
- De-Feng Li
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), No. 1017, Dongmen North Road, Luohu District, Shenzhen 518020, Guangdong, China.
| | - Mei-Feng Yang
- Department of Hematology, Yantian District People's Hospital, Shenzhen 518020, Guangdong, China
| | - Hao-Ming Xu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510030, China
| | - Min-Zheng Zhu
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510030, China
| | - Yuan Zhang
- Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou 516000, Guangdong, China
| | - Cheng-Mei Tian
- Department of Emergency, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, Guangdong, China
| | - Yu-Qiang Nie
- Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou 510030, China
| | - Jian-Yao Wang
- Department of General Surgery, Shenzhen Children's Hospital, No. 7019, Yitian Road, Futian District, Shenzhen 518026, Guangdong, China.
| | - Yu-Jie Liang
- Shenzhen Kangning Hospital, No. 1080, Cuizu Road, Luohu District, Shenzhen 518020, Guangdong, China.
| | - Jun Yao
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), No. 1017, Dongmen North Road, Luohu District, Shenzhen 518020, Guangdong, China.
| | - Li-Sheng Wang
- Department of Gastroenterology, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University, the First Affiliated Hospital, Southern University of Science and Technology), No. 1017, Dongmen North Road, Luohu District, Shenzhen 518020, Guangdong, China.
| |
Collapse
|
|
12
|
Wang C, Yang J, Chang W. PLGA-based microspheres containing ropivacaine and betamethasone for sciatic nerve block in mice. Pharm Dev Technol 2022; 27:503-510. [PMID: 35653620 DOI: 10.1080/10837450.2020.1871011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
The aim of the present study was to develop Poly (lactic-co-glycolic acid) (PLGA)-based microspheres containing ropivacaine and betamethasone (RPC/BTM PLGA MS) by emulsion-solvent evaporation method. RPC/BTM PLGA MS were characterized by physical properties, such as morphology and particle size, and in vitro drug release. In addition, in vivo pharmacokinetics and pharmacodynamics of RPC/BTM PLGA MS were also investigated. The prepared RPC/BTM PLGA MS was suitable for local injection with a well-dispersed spherical shape, high stability, and high encapsulation efficiency. The mean diameter was 14.8 ± 1.2 µm and the polydispersity index (PDI) was 0.32 ± 0.04. In an in vitro study of drug release, it can be concluded that the RPC/BTM PLGA MS exhibited sustained and long-term release properties for 16 days. Furthermore, the result of an in vivo study indicated that the RPC/BTM PLGA MS had sustained release effect and the pharmacodynamics result showed that preparing RPC/BTM PLGA MS as microsphere preparation could not only extend the drug effect time but also prolong the duration of local anesthetics compared with the common RPC PLGA MS.
Collapse
Affiliation(s)
- Chunquan Wang
- Department of intensive care unit, the Ninth People's Hospital of Chongqing, Chongqing, China
| | - Jinjun Yang
- Department of intensive care unit, the Ninth People's Hospital of Chongqing, Chongqing, China
| | - Weimin Chang
- Department of intensive care unit, the Ninth People's Hospital of Chongqing, Chongqing, China
| |
Collapse
|
|
13
|
Yasmin F, Najeeb H, Shaikh S, Hasanain M, Naeem U, Moeed A, Koritala T, Hasan S, Surani S. Novel drug delivery systems for inflammatory bowel disease. World J Gastroenterol 2022; 28:1922-1933. [PMID: 35664964 PMCID: PMC9150062 DOI: 10.3748/wjg.v28.i18.1922] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 01/22/2022] [Accepted: 03/26/2022] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic illness characterized by relapsing inflammation of the intestines. The disorder is stratified according to the severity and is marked by its two main phenotypical representations: Ulcerative colitis and Crohn's disease. Pathogenesis of the disease is ambiguous and is expected to have interactivity between genetic disposition, environmental factors such as bacterial agents, and dysregulated immune response. Treatment for IBD aims to reduce symptom extent and severity and halt disease progression. The mainstay drugs have been 5-aminosalicylates (5-ASAs), corticosteroids, and immunosuppressive agents. Parenteral, oral and rectal routes are the conventional methods of drug delivery, and among all, oral administration is most widely adopted. However, problems of systematic drug reactions and low specificity in delivering drugs to the inflamed sites have emerged with these regular routes of delivery. Novel drug delivery systems have been introduced to overcome several therapeutic obstacles and for localized drug delivery to target tissues. Enteric-coated microneedle pills, various nano-drug delivery techniques, prodrug systems, lipid-based vesicular systems, hybrid drug delivery systems, and biologic drug delivery systems constitute some of these novel methods. Microneedles are painless, they dislodge their content at the affected site, and their release can be prolonged. Recombinant bacteria such as genetically engineered Lactococcus Lactis and eukaryotic cells, including GM immune cells and red blood cells as nanoparticle carriers, can be plausible delivery methods when evaluating biologic systems. Nano-particle drug delivery systems consisting of various techniques are also employed as nanoparticles can penetrate through inflamed regions and adhere to the thick mucus of the diseased site. Prodrug systems such as 5-ASAs formulations or their derivatives are effective in reducing colonic damage. Liposomes can be modified with both hydrophilic and lipophilic particles and act as lipid-based vesicular systems, while hybrid drug delivery systems containing an internal nanoparticle section for loading drugs are potential routes too. Leukosomes are also considered as possible carrier systems, and results from mouse models have revealed that they control anti- and pro-inflammatory molecules.
Collapse
Affiliation(s)
- Farah Yasmin
- Department of Medicine, Dow University of Health Science, Karachi 74200, Pakistan
| | - Hala Najeeb
- Department of Medicine, Dow University of Health Science, Karachi 74200, Pakistan
| | - Shehryar Shaikh
- Department of Medicine, Dow OJha University Hospital, Karachi 74200, Pakistan
| | - Muhammad Hasanain
- Department of Medicine, Dow University of Health Science, Karachi 74200, Pakistan
| | - Unaiza Naeem
- Department of Medicine, Dow University of Health Science, Karachi 74200, Pakistan
| | - Abdul Moeed
- Department of Medicine, Dow University of Health Science, Karachi 74200, Pakistan
| | - Thoyaja Koritala
- Department of Medicine, Mayo Clinic Health System, Mankato, MN 56001, United States
| | - Syedadeel Hasan
- Department of Medicine, University of Louisville, Louisville, KY 40292, United States
| | - Salim Surani
- Department of Medicine, Texas A&M University, College Station, TX 77843, United States
- Department of Anesthesiology, Mayo Clinic, Rochester, MN 55901, United States
| |
Collapse
|
|
14
|
Kotla NG, Singh R, Baby BV, Rasala S, Rasool J, Hynes SO, Martin D, Egan LJ, Vemula PK, Jala VR, Rochev Y, Pandit A. Inflammation-specific targeted carriers for local drug delivery to inflammatory bowel disease. Biomaterials 2022; 281:121364. [DOI: 10.1016/j.biomaterials.2022.121364] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 12/27/2021] [Accepted: 01/03/2022] [Indexed: 12/15/2022]
|
|
15
|
Lee Y, Kamada N, Moon JJ. Oral nanomedicine for modulating immunity, intestinal barrier functions, and gut microbiome. Adv Drug Deliv Rev 2021; 179:114021. [PMID: 34710529 PMCID: PMC8665886 DOI: 10.1016/j.addr.2021.114021] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 10/17/2021] [Accepted: 10/20/2021] [Indexed: 12/12/2022]
Abstract
The gastrointestinal tract (GIT) affects not only local diseases in the GIT but also various systemic diseases. Factors that can affect the health and disease of both GIT and the human body include 1) the mucosal immune system composed of the gut-associated lymphoid tissues and the lamina propria, 2) the intestinal barrier composed of mucus and intestinal epithelium, and 3) the gut microbiota. Selective delivery of drugs, including antigens, immune-modulators, intestinal barrier enhancers, and gut-microbiome manipulators, has shown promising results for oral vaccines, immune tolerance, treatment of inflammatory bowel diseases, and other systemic diseases, including cancer. However, physicochemical and biological barriers of the GIT present significant challenges for successful translation. With the advances of novel nanomaterials, oral nanomedicine has emerged as an attractive option to not only overcome these barriers but also to selectively deliver drugs to the target sites in GIT. In this review, we discuss the GIT factors and physicochemical and biological barriers in the GIT. Furthermore, we present the recent progress of oral nanomedicine for oral vaccines, immune tolerance, and anti-inflammation therapies. We also discuss recent advances in oral nanomedicine designed to fortify the intestinal barrier functions and modulate the gut microbiota and microbial metabolites. Finally, we opine about the future directions of oral nano-immunotherapy.
Collapse
Affiliation(s)
- Yonghyun Lee
- Department of Pharmacy, College of Pharmacy, Ewha Womans University, Seoul 03760, South Korea; Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, South Korea.
| | - Nobuhiko Kamada
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, 1150 W. Medical Center Drive, Ann Arbor, MI 48109, USA
| | - James J Moon
- Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI 48109 USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109 USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109 USA.
| |
Collapse
|
|
16
|
Zu M, Ma Y, Cannup B, Xie D, Jung Y, Zhang J, Yang C, Gao F, Merlin D, Xiao B. Oral delivery of natural active small molecules by polymeric nanoparticles for the treatment of inflammatory bowel diseases. Adv Drug Deliv Rev 2021; 176:113887. [PMID: 34314785 DOI: 10.1016/j.addr.2021.113887] [Citation(s) in RCA: 105] [Impact Index Per Article: 26.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 06/27/2021] [Accepted: 07/18/2021] [Indexed: 12/11/2022]
Abstract
The incidence of inflammatory bowel disease (IBD) is rapidly rising throughout the world. Although tremendous efforts have been made, limited therapeutics are available for IBD management. Natural active small molecules (NASMs), which are a gift of nature to humanity, have been widely used in the prevention and alleviation of IBD; they have numerous advantageous features, including excellent biocompatibility, pharmacological activity, and mass production potential. Oral route is the most common and acceptable approach for drug administration, but the clinical application of NASMs in IBD treatment via oral route has been seriously restricted by their inherent limitations such as high hydrophobicity, instability, and poor bioavailability. With the development of nanotechnology, polymeric nanoparticles (NPs) have provided a promising platform that can efficiently encapsulate versatile NASMs, overcome multiple drug delivery barriers, and orally deliver the loaded NASMs to targeted tissues or cells while enhancing their stability and bioavailability. Thus, NPs can enhance the preventive and therapeutic effects of NASMs against IBD. Herein, we summarize the recent knowledge about polymeric matrix-based carriers, targeting ligands for drug delivery, and NASMs. We also discuss the current challenges and future developmental directions.
Collapse
Affiliation(s)
- Menghang Zu
- State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Beibei, Chongqing 400715, China
| | - Ya Ma
- State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Beibei, Chongqing 400715, China
| | - Brandon Cannup
- Institute for Biomedical Sciences, Digestive Disease Research Group, Georgia State University, Atlanta, Georgia 30302, United States
| | - Dengchao Xie
- State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Beibei, Chongqing 400715, China; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China; College of Food Science, Southwest University, Beibei, Chongqing 400715, China
| | - Yunjin Jung
- College of Pharmacy, Pusan National University, Geumjeong-gu, Busan 46241, South Korea
| | - Jinming Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China
| | - Chunhua Yang
- Institute for Biomedical Sciences, Digestive Disease Research Group, Georgia State University, Atlanta, Georgia 30302, United States; Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, United States
| | - Fei Gao
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.
| | - Didier Merlin
- Institute for Biomedical Sciences, Digestive Disease Research Group, Georgia State University, Atlanta, Georgia 30302, United States; Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, United States.
| | - Bo Xiao
- State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Beibei, Chongqing 400715, China.
| |
Collapse
|
|
17
|
Liu P, Gao C, Chen H, Vong CT, Wu X, Tang X, Wang S, Wang Y. Receptor-mediated targeted drug delivery systems for treatment of inflammatory bowel disease: Opportunities and emerging strategies. Acta Pharm Sin B 2021; 11:2798-2818. [PMID: 34589398 PMCID: PMC8463263 DOI: 10.1016/j.apsb.2020.11.003] [Citation(s) in RCA: 82] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 10/01/2020] [Accepted: 10/14/2020] [Indexed: 02/08/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic intestinal disease with painful clinical manifestations and high risks of cancerization. With no curative therapy for IBD at present, the development of effective therapeutics is highly advocated. Drug delivery systems have been extensively studied to transmit therapeutics to inflamed colon sites through the enhanced permeability and retention (EPR) effect caused by the inflammation. However, the drug still could not achieve effective concentration value that merely utilized on EPR effect and display better therapeutic efficacy in the inflamed region because of nontargeted drug release. Substantial researches have shown that some specific receptors and cell adhesion molecules highly expresses on the surface of colonic endothelial and/or immune cells when IBD occurs, ligand-modified drug delivery systems targeting such receptors and cell adhesion molecules can specifically deliver drug into inflamed sites and obtain great curative effects. This review introduces the overexpressed receptors and cell adhesion molecules in inflamed colon sites and retrospects the drug delivery systems functionalized by related ligands. Finally, challenges and future directions in this field are presented to advance the development of the receptor-mediated targeted drug delivery systems for the therapy of IBD.
Collapse
Key Words
- ACQ, aggregation-caused quenching
- ADR, adverse drug reaction
- AIE, aggregation-induced emission
- Active target
- BSA, bovine serum albumin
- CAM, cell adhesion molecule
- CD, Crohn's disease
- CRD, cysteine-rich domain
- CS, chondroitin sulfate
- CT, computed tomography
- CTLD, c-type lectin-like domain
- Cell adhesion molecule
- Crohn's disease
- DCs, dendritic cells
- DSS, dextran sulfate sodium salt
- Drug delivery
- EGF, epidermal growth factor
- EPR, enhanced permeability and retention
- FNII, fibronectin type II domain
- FR, folate receptor
- FRET, fluorescence resonance energy transfer
- GIT, gastrointestinal tract
- HA, hyaluronic acid
- HUVEC, human umbilical vein endothelial cells
- IBD, inflammatory bowel disease
- ICAM, intercellular adhesion molecule
- Inflammatory bowel disease
- LMWC, low molecular weight chitosan
- LPS, lipopolysaccharide
- MAP4K4, mitogen-activated protein kinase kinase kinase kinase 4
- MGL, macrophage galactose lectin
- MPO, myeloperoxidase
- MPS, mononuclear phagocyte system
- MR, mannose receptor
- MRI, magnetic resonance imaging
- PAMAM, poly(amidoamine)
- PEI, polyethylenimine
- PSGL-1, P-selectin glycoprotein ligand-1
- PepT1, peptide transporter 1
- QDs, quantum dots
- RES, reticuloendothelial system
- Receptor-mediated target
- Targeted therapy
- TfR, transferrin receptor
- UC, ulcerative colitis
- Ulcerative colitis
- VCAM, vascular cell adhesion molecule
Collapse
|
|
18
|
Chen F, Liu Q, Xiong Y, Xu L. Current Strategies and Potential Prospects of Nanomedicine-Mediated Therapy in Inflammatory Bowel Disease. Int J Nanomedicine 2021; 16:4225-4237. [PMID: 34188471 PMCID: PMC8236271 DOI: 10.2147/ijn.s310952] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 06/07/2021] [Indexed: 12/12/2022] Open
Abstract
Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis are highly debilitating. IBDs are associated with the imbalance of inflammatory mediators within the inflamed bowel. Conventional drugs for IBD treatment include anti-inflammatory medications and immune suppressants. However, they suffer from a lack of bioavailability and high dose-induced systemic side effects. Nanoparticle (NP)-derived therapy improves therapeutic efficacy and increases targeting specificity. Recent studies have shown that nanomedicines, based on bowel disease's pathophysiology, are a fast-growing field. NPs can prolong the circulation period and reduce side effects by improving drug encapsulation and targeted delivery. Here, this review summarizes various IBD therapies with a focus on NP-derived applications, whereas their challenges and future perspectives have also been discussed.
Collapse
Affiliation(s)
- Fengqian Chen
- Translational Research Program, Department of Anesthesiology and Center for Shock Trauma Anesthesiology Research, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Qi Liu
- Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA
| | - Yang Xiong
- College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310053, People’s Republic of China
| | - Li Xu
- Department of Anorectal Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310006, People’s Republic of China
| |
Collapse
|
|
19
|
Minakshi P, Kumar R, Ghosh M, Brar B, Barnela M, Lakhani P. Application of Polymeric Nano-Materials in Management of Inflammatory Bowel Disease. Curr Top Med Chem 2021; 20:982-1008. [PMID: 32196449 DOI: 10.2174/1568026620666200320113322] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 01/25/2020] [Accepted: 02/24/2020] [Indexed: 02/06/2023]
Abstract
Inflammatory Bowel Disease (IBD) is an umbrella term used to describe disorders that involve Crohn's disease (CD), ulcerative colitis (UC) and pouchitis. The disease occurrence is more prevalent in the working group population which not only hampers the well being of an individual but also has negative economical impact on society. The current drug regime used therapy is very costly owing to the chronic nature of the disease leading to several side effects. The condition gets more aggravated due to the lower concentration of drug at the desired site. Therefore, in the present scenario, a therapy is needed which can maximize efficacy, adhere to quality of life, minimize toxicity and doses, be helpful in maintaining and stimulating physical growth of mucosa with minimum disease complications. In this aspect, nanotechnology intervention is one promising field as it can act as a carrier to reduce toxicity, doses and frequency which in turn help in faster recovery. Moreover, nanomedicine and nanodiagnostic techniques will further open a new window for treatment in understanding pathogenesis along with better diagnosis which is poorly understood till now. Therefore the present review is more focused on recent advancements in IBD in the application of nanotechnology.
Collapse
Affiliation(s)
- Prasad Minakshi
- Department of Animal Biotechnology, LLR University of Veterinary and Animal Sciences, Hisar-125001, Haryana, India
| | - Rajesh Kumar
- Department of Veterinary Physiology & Biochemistry, LUVAS, Hisar-125 004, India
| | - Mayukh Ghosh
- Department of Veterinary Physiology and Biochemistry, RGSC, Banaras Hindu University, Mirzapur (UP) - 231001, India
| | - Basanti Brar
- Department of Animal Biotechnology, LLR University of Veterinary and Animal Sciences, Hisar-125001, Haryana, India
| | - Manju Barnela
- Department of Nano & Biotechnology, Guru Jambheshwar University, Hisar-125001, Haryana, India
| | - Preeti Lakhani
- Department of Veterinary Physiology & Biochemistry, LUVAS, Hisar-125 004, India
| |
Collapse
|
|
20
|
Nanoparticle-based therapeutics of inflammatory bowel diseases: a narrative review of the current state and prospects. JOURNAL OF BIO-X RESEARCH 2020. [DOI: 10.1097/jbr.0000000000000078] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
|
|
21
|
Li X, Lu C, Yang Y, Yu C, Rao Y. Site-specific targeted drug delivery systems for the treatment of inflammatory bowel disease. Biomed Pharmacother 2020; 129:110486. [PMID: 32768972 DOI: 10.1016/j.biopha.2020.110486] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 06/30/2020] [Accepted: 06/30/2020] [Indexed: 12/14/2022] Open
Abstract
Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis and manifests as a complex and dysregulated immune response. To date, there is no cure for IBD; thus, lifelong administration of maintenance drugs is often necessary. Since conventional IBD treatment strategies do not target the sites of inflammation, only limited efficacy is observed with their use. Moreover, the possibility of severe side effects resulting from systemic drug redistribution is high when conventional drug treatments are used. Therefore, a straightforward disease-targeted drug delivery system is desirable. Based on the pathophysiological changes associated with IBD, novel site-specific targeted drug delivery strategies that deliver drugs directly to the inflammation sites can enhance drug accumulation and decrease side effects. This review summarizes novel inflammation targeted delivery systems in the management of IBD. It also discusses the challenges and new perspectives in this field.
Collapse
Affiliation(s)
- Xin Li
- Department of Pharmacology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Chao Lu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Yanyan Yang
- Department of Pharmacology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Chaohui Yu
- Department of Gastroenterology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
| | - Yuefeng Rao
- Department of Pharmacology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China.
| |
Collapse
|
|
22
|
Hua S. Advances in Oral Drug Delivery for Regional Targeting in the Gastrointestinal Tract - Influence of Physiological, Pathophysiological and Pharmaceutical Factors. Front Pharmacol 2020; 11:524. [PMID: 32425781 PMCID: PMC7212533 DOI: 10.3389/fphar.2020.00524] [Citation(s) in RCA: 227] [Impact Index Per Article: 45.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Accepted: 04/03/2020] [Indexed: 12/22/2022] Open
Abstract
The oral route is by far the most common route of drug administration in the gastrointestinal tract and can be used for both systemic drug delivery and for treating local gastrointestinal diseases. It is the most preferred route by patients, due to its advantages, such as ease of use, non-invasiveness, and convenience for self-administration. Formulations can also be designed to enhance drug delivery to specific regions in the upper or lower gastrointestinal tract. Despite the clear advantages offered by the oral route, drug delivery can be challenging as the human gastrointestinal tract is complex and displays a number of physiological barriers that affect drug delivery. Among these challenges are poor drug stability, poor drug solubility, and low drug permeability across the mucosal barriers. Attempts to overcome these issues have focused on improved understanding of the physiology of the gastrointestinal tract in both healthy and diseased states. Innovative pharmaceutical approaches have also been explored to improve regional drug targeting in the gastrointestinal tract, including nanoparticulate formulations. This review will discuss the physiological, pathophysiological, and pharmaceutical considerations influencing drug delivery for the oral route of administration, as well as the conventional and novel drug delivery approaches. The translational challenges and development aspects of novel formulations will also be addressed.
Collapse
Affiliation(s)
- Susan Hua
- Therapeutic Targeting Research Group, School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia
- Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| |
Collapse
|
|
23
|
Zhang X, Song H, Canup BSB, Xiao B. Orally delivered targeted nanotherapeutics for the treatment of colorectal cancer. Expert Opin Drug Deliv 2020; 17:781-790. [PMID: 32237921 DOI: 10.1080/17425247.2020.1748005] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Colorectal cancer (CRC), the third-most common malignancy, has high morbidity and mortality. Oral nanotherapeutics have emerged as a promising strategy to improve the therapeutic outcomes and alleviate the adverse effects of drugs in CRC treatment. AREAS COVERED In this review, we introduce the beneficial features of oral drug administration for CRC therapy, and further address the three basic elements of nanotherapeutics, namely, therapeutic agents, carrier materials, and targeting ligands. In addition, we also discuss the potentials of the new emerging technologies (e.g., immunotherapy, gene editing and microbiota manipulation) in the treatment of CRC. EXPERT OPINION Orally delivered targeted nanotherapeutics represent a promising strategy toward the efficient treatment of CRC. Although the current oral nanotherapeutics exert better therapeutic outcomes than the traditional drug formulations, their application has been restricted by drug resistance, tumor metastasis, and biosafety. Therefore, it is necessary to exploit new nanotherapeutics in the aspects of their three basic elements, and combine the new emerging technologies to those nanotherapeutics for CRC treatment.
Collapse
Affiliation(s)
- Xueqing Zhang
- State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University , Beibei, P. R. China
| | - Heliang Song
- Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University , Atlanta, GA, USA
| | - Brandon S B Canup
- Department of Chemistry, Center for Diagnostics and Therapeutics, Georgia State University , Atlanta, GA, USA
| | - Bo Xiao
- State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University , Beibei, P. R. China.,Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Biotechnology, Southwest University , Chongqing, P. R. China
| |
Collapse
|
|
24
|
Zu M, Song H, Zhang J, Chen Q, Deng S, Canup BS, Yuan Y, Xiao B. Lycium barbarum lipid-based edible nanoparticles protect against experimental colitis. Colloids Surf B Biointerfaces 2020; 187:110747. [DOI: 10.1016/j.colsurfb.2019.110747] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Revised: 11/26/2019] [Accepted: 12/19/2019] [Indexed: 02/07/2023]
|
|
25
|
de Souza AB, Chaud MV, Santana MHA. Hyaluronic acid behavior in oral administration and perspectives for nanotechnology-based formulations: A review. Carbohydr Polym 2019; 222:115001. [PMID: 31320101 DOI: 10.1016/j.carbpol.2019.115001] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2019] [Revised: 06/15/2019] [Accepted: 06/16/2019] [Indexed: 12/17/2022]
|
|
26
|
Kotla NG, Rana S, Sivaraman G, Sunnapu O, Vemula PK, Pandit A, Rochev Y. Bioresponsive drug delivery systems in intestinal inflammation: State-of-the-art and future perspectives. Adv Drug Deliv Rev 2019; 146:248-266. [PMID: 29966684 DOI: 10.1016/j.addr.2018.06.021] [Citation(s) in RCA: 142] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2018] [Revised: 05/27/2018] [Accepted: 06/25/2018] [Indexed: 02/07/2023]
Abstract
Oral colon-specific delivery systems emerged as the main therapeutic cargos by making a significant impact in the field of modern medicine for local drug delivery in intestinal inflammation. The site-specific delivery of therapeutics (aminosalicylates, glucocorticoids, biologics) to the ulcerative mucus tissue can provide prominent advantages in mucosal healing (MH). Attaining gut mucosal healing and anti-fibrosis are main treatment outcomes in inflammatory bowel disease (IBD). The pharmaceutical strategies that are commonly used to achieve a colon-specific drug delivery system include time, pH-dependent polymer coating, prodrug, colonic microbiota-activated delivery systems and a combination of these approaches. Amongst the different approaches reported, the use of biodegradable polysaccharide coated systems holds great promise in delivering drugs to the ulcerative regions. The present review focuses on major physiological gastro-intestinal tract challenges involved in altering the pharmacokinetics of delivery systems, pathophysiology of MH and fibrosis, reported drug-polysaccharide cargos and focusing on conventional to advanced disease responsive delivery strategies, highlighting their limitations and future perspectives in intestinal inflammation therapy.
Collapse
Affiliation(s)
- Niranjan G Kotla
- Centre for Research in Medical Devices (CÚRAM), National University of Ireland Galway, Newcastle, Galway, Ireland.
| | - Shubhasmin Rana
- Centre for Research in Medical Devices (CÚRAM), National University of Ireland Galway, Newcastle, Galway, Ireland
| | - Gandhi Sivaraman
- Institute for Stem Cell Biology and Regenerative Medicine, GKVK Campus, Bengaluru 560062, India
| | - Omprakash Sunnapu
- Institute for Stem Cell Biology and Regenerative Medicine, GKVK Campus, Bengaluru 560062, India
| | - Praveen K Vemula
- Institute for Stem Cell Biology and Regenerative Medicine, GKVK Campus, Bengaluru 560062, India
| | - Abhay Pandit
- Centre for Research in Medical Devices (CÚRAM), National University of Ireland Galway, Newcastle, Galway, Ireland
| | - Yury Rochev
- Centre for Research in Medical Devices (CÚRAM), National University of Ireland Galway, Newcastle, Galway, Ireland; Sechenov First Moscow State Medical University, Institute for Regenerative Medicine, Moscow, Russian Federation.
| |
Collapse
|
|
27
|
Zhou H, Qian H. Preparation and characterization of pH-sensitive nanoparticles of budesonide for the treatment of ulcerative colitis. DRUG DESIGN DEVELOPMENT AND THERAPY 2018; 12:2601-2609. [PMID: 30174414 PMCID: PMC6110634 DOI: 10.2147/dddt.s170676] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Objective The aim of this study was to develop pH sensitive nanoparticles of budesonide for the treatment of ulcerative colitis. Methods The NPs system was characterized by the transmission electron microscopy (TEM), particle size, drug loading and encapsulation efficiency. In addition, in vitro drug release prop-erties and pharmacokinetics were also investigated in detail. The optimized formulation was examined for its in-vivo targeting potential using 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in a rat model. Results Dynamic light-scattering results showed that the particle size of budesonide-Eudragit S100/poly(lactic-co-glycolic acid) nanoparticles was around 110.5 nm, with a polydispersity index of 0.098. Transmission electron microscopy images showed that BUD-ES100/PLGA NPs were spherical with uniform size and relatively smooth surfaces. In vitro release showed that BUD-ES100/PLGA NPs required minimal release of drugs during its transit in the stomach and the upper small intestine to ensure that a maximum dose reached the colon. After the pharma-codynamic treatment, the myeloperoxidase value of BUD-ES100/PLGA NPs was close to the normal group. The histopathological examination of rectum showed that no sign of damages such as epithelial necrosis and sloughing epithelial cells was detected. Conclusion Our findings suggested that BUD-ES100/PLGA NPs were a promising alternative to single pH-dependent systems for colitis therapy.
Collapse
Affiliation(s)
- Hong Zhou
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, People's Republic of China, .,Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, People's Republic of China
| | - Haixin Qian
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, People's Republic of China,
| |
Collapse
|
|
28
|
Advances in Pharmaceutical Strategies Enhancing the Efficiencies of Oral Colon-Targeted Delivery Systems in Inflammatory Bowel Disease. Molecules 2018; 23:molecules23071622. [PMID: 29973488 PMCID: PMC6099616 DOI: 10.3390/molecules23071622] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2018] [Revised: 06/25/2018] [Accepted: 06/28/2018] [Indexed: 12/15/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a common disease characterized by chronic inflammation in gastrointestinal tracts, which is primarily treated by administering anti-inflammatory and immunosuppressive drugs that inhibit the burden of intestinal inflammation and improve disease-related symptoms. However, the established therapeutic strategy has limited therapeutic efficacy and adverse drug reactions. Therefore, new disease-targeting drug-delivery strategies to develop more effective treatments are urgent. This review provides an overview of the drug-targeting strategies that can be used to treat IBD, and our recent attempts on the colon-specific delivery system (Pae-SME-CSC) with a paeonol-loaded self-microemulsion (Pae-SMEDDS) are introduced.
Collapse
|
|
29
|
Zhang M, Merlin D. Nanoparticle-Based Oral Drug Delivery Systems Targeting the Colon for Treatment of Ulcerative Colitis. Inflamm Bowel Dis 2018; 24:1401-1415. [PMID: 29788186 PMCID: PMC6085987 DOI: 10.1093/ibd/izy123] [Citation(s) in RCA: 121] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2017] [Indexed: 12/17/2022]
Abstract
10.1093/ibd/izy123_video1izy123.video15786481867001.
Collapse
Affiliation(s)
- Mingzhen Zhang
- Institute for Biomedical Sciences, Digestive Diseases Research Group, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia
| | - Didier Merlin
- Institute for Biomedical Sciences, Digestive Diseases Research Group, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia
- Alanta Veterans Affairs Medical Center, Decatur, Georgia
| |
Collapse
|
|
30
|
Zhang M, Xu C, Liu D, Han MK, Wang L, Merlin D. Oral Delivery of Nanoparticles Loaded With Ginger Active Compound, 6-Shogaol, Attenuates Ulcerative Colitis and Promotes Wound Healing in a Murine Model of Ulcerative Colitis. J Crohns Colitis 2018; 12:217-229. [PMID: 28961808 PMCID: PMC5881712 DOI: 10.1093/ecco-jcc/jjx115] [Citation(s) in RCA: 145] [Impact Index Per Article: 20.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2017] [Accepted: 08/15/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Oral drug delivery is the most attractive pathway for ulcerative colitis [UC] therapy, since it has many advantages. However, this strategy has encountered many challenges, including the instability of drugs in the gastrointestinal tract [GT], low targeting of disease tissues, and severe adverse effects. Nanoparticles capable of colitis tissue-targeted delivery and site-specific drug release may offer a unique and therapeutically effective system that addresses these formidable challenges. METHODS We used a versatile single-step surface-functionalising technique to prepare PLGA/PLA-PEG-FA nanoparticles loaded with the ginger active compound, 6-shogaol [NPs-PEG-FA/6-shogaol]. The therapeutic efficacy of NPs-PEG-FA/6-shogaol was evaluated in the well-established mouse model of dextran sulphate sodium [DSS]-induced colitis. RESULTS NPs-PEG-FA exhibited very good biocompatibility both in vitro and in vivo. Subsequent cellular uptake experiments demonstrated that NPs-PEG-FA could undergo efficient receptor-mediated uptake by colon-26 cells and activated Raw 264.7 macrophage cells. In vivo, oral administration of NPs-PEG-FA/6-shogaol encapsulated in a hydrogel system [chitosan/alginate] significantly alleviated colitis symptoms and accelerated colitis wound repair in DSS-treated mice by regulating the expression levels of pro-inflammatory [TNF-α, IL-6, IL-1β, and iNOS] and anti-inflammatory [Nrf-2 and HO-1] factors. CONCLUSIONS Our study demonstrates a convenient, orally administered 6-shogaol drug delivery system that effectively targets colitis tissue, alleviates colitis symptoms, and accelerates colitis wound repair. This system may represent a promising therapeutic approach for treating inflammatory bowel disease [IBD].
Collapse
Affiliation(s)
- Mingzhen Zhang
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA,Corresponding author: Mingzhen Zhang, Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA. Tel.: +1 [404] 413 3597; fax: +1 [404] 413 3580;
| | - Changlong Xu
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA,Department of Gastroenterology, 2nd Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Zhejiang, P. R. China
| | - Dandan Liu
- Department of Chemistry, Georgia State University, Atlanta, GA, USA
| | - Moon Kwon Han
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA
| | - Lixin Wang
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA,Atlanta Veterans Affairs Medical Center, Decatur, GA, USA
| | - Didier Merlin
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA,Atlanta Veterans Affairs Medical Center, Decatur, GA, USA
| |
Collapse
|
|
31
|
Zhang S, Langer R, Traverso G. Nanoparticulate Drug Delivery Systems Targeting Inflammation for Treatment of Inflammatory Bowel Disease. NANO TODAY 2017; 16:82-96. [PMID: 31186671 PMCID: PMC6557461 DOI: 10.1016/j.nantod.2017.08.006] [Citation(s) in RCA: 143] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Inflammatory bowel disease (IBD) is a chronic, idiopathic inflammatory set of conditions that can affect the entire gastrointestinal (GI) tract and is associated with an increased risk of colorectal cancer. To date there is no curative therapy for IBD; therefore life-long medication can be necessary for IBD management if surgery is to be avoided. Drug delivery systems specific to the colon have improved IBD treatment and several such systems are available to patients. However, current delivery systems for IBD do not target drugs to the site of inflammation, which leads to frequent dosing and potentially severe side effects that can adversely impact patients' adherence to medication. There is a need for novel drug delivery systems that can target drugs to the site of inflammation, prolong local drug availability, improve therapeutic efficacy, and reduce drug side effects. Nanoparticulate (NP) systems are attractive in designing targeted drug delivery systems for the treatment of IBD because of their unique physicochemical properties and capability of targeting the site of disease. This review analyzes the microenvironment at the site of inflammation in IBD, highlighting the pathophysiological features as possible cues for targeted delivery; discusses different strategies and mechanisms of NP targeting IBD, including size-, charge-, ligand-receptor, degradation- and microbiome-mediated approaches; and summarizes recent progress on using NPs towards improved therapies for IBD. Finally, challenges and future directions in this field are presented to advance the development of targeted drug delivery for IBD treatment.
Collapse
Affiliation(s)
- Sufeng Zhang
- The David H. Koch Institute for Integrative Cancer Research and Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
| | - Robert Langer
- The David H. Koch Institute for Integrative Cancer Research and Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
- Media Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
- Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
| | - Giovanni Traverso
- Media Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
- Division of Gastroenterology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115
| |
Collapse
|
|
32
|
Chen Q, Xiao B, Merlin D. Nanotherapeutics for the treatment of inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2017; 11:495-497. [PMID: 28317404 DOI: 10.1080/17474124.2017.1309282] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Affiliation(s)
- Qiubing Chen
- a Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy , Southwest University , Chongqing , P. R. China
| | - Bo Xiao
- a Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy , Southwest University , Chongqing , P. R. China.,b Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics , Georgia State University , Atlanta , GA , USA
| | - Didier Merlin
- b Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics , Georgia State University , Atlanta , GA , USA.,c Atlanta Veterans Affairs Medical Center , Decatur , GA , USA
| |
Collapse
|
|
33
|
Xiao B, Xu Z, Viennois E, Zhang Y, Zhang Z, Zhang M, Han MK, Kang Y, Merlin D. Orally Targeted Delivery of Tripeptide KPV via Hyaluronic Acid-Functionalized Nanoparticles Efficiently Alleviates Ulcerative Colitis. Mol Ther 2017; 25:1628-1640. [PMID: 28143741 DOI: 10.1016/j.ymthe.2016.11.020] [Citation(s) in RCA: 141] [Impact Index Per Article: 17.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2016] [Revised: 10/23/2016] [Accepted: 11/27/2016] [Indexed: 12/22/2022] Open
Abstract
Overcoming adverse effects and selectively delivering drug to target cells are two major challenges in the treatment of ulcerative colitis (UC). Lysine-proline-valine (KPV), a naturally occurring tripeptide, has been shown to attenuate the inflammatory responses of colonic cells. Here, we loaded KPV into hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant HA-KPV-NPs had a desirable particle size (∼272.3 nm) and a slightly negative zeta potential (∼-5.3 mV). These NPs successfully mediated the targeted delivery of KPV to key UC therapy-related cells (colonic epithelial cells and macrophages). In addition, these KPV-loaded NPs appear to be nontoxic and biocompatible with intestinal cells. Intriguingly, we found that HA-KPV-NPs exert combined effects against UC by both accelerating mucosal healing and alleviating inflammation. Oral administration of HA-KPV-NPs encapsulated in a hydrogel (chitosan/alginate) exhibited a much stronger capacity to prevent mucosa damage and downregulate TNF-α, thus they showed a much better therapeutic efficacy against UC in a mouse model, compared with a KPV-NP/hydrogel system. These results collectively demonstrate that our HA-KPV-NP/hydrogel system has the capacity to release HA-KPV-NPs in the colonic lumen and that these NPs subsequently penetrate into colitis tissues and enable KPV to be internalized into target cells, thereby alleviating UC.
Collapse
Affiliation(s)
- Bo Xiao
- Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, People's Republic of China; Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA.
| | - Zhigang Xu
- Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, People's Republic of China
| | - Emilie Viennois
- Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA
| | - Yuchen Zhang
- Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA
| | - Zhan Zhang
- Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA
| | - Mingzhen Zhang
- Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA
| | - Moon Kwon Han
- Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA
| | - Yuejun Kang
- Institute for Clean Energy and Advanced Materials, Faculty of Materials and Energy, Southwest University, Chongqing 400715, People's Republic of China
| | - Didier Merlin
- Institute for Biomedical Sciences, Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302, USA; Atlanta Veterans Affairs Medical Center, Decatur, GA 30033, USA
| |
Collapse
|
|
34
|
Xiao B, Zhang Z, Viennois E, Kang Y, Zhang M, Han MK, Chen J, Merlin D. Combination Therapy for Ulcerative Colitis: Orally Targeted Nanoparticles Prevent Mucosal Damage and Relieve Inflammation. Am J Cancer Res 2016; 6:2250-2266. [PMID: 27924161 PMCID: PMC5135446 DOI: 10.7150/thno.15710] [Citation(s) in RCA: 174] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2016] [Accepted: 08/12/2016] [Indexed: 02/06/2023] Open
Abstract
Combination therapy is an emerging strategy that is under intensive preclinical investigation for the treatment of various diseases. CD98 is highly overexpressed on the surfaces of epithelial cells and macrophages in the colon tissue with ulcerative colitis (UC), which is usually associated with mucosal damage and inflammation. We previously proved that CD98 siRNA (siCD98)-induced down-regulation of CD98 in colitis tissue decreased the severity of UC to a certain extent. In an effort to further improve the therapeutic efficacy, we aim to simultaneously deliver siCD98 in combination with a potent anti-inflammatory agent, curcumin (CUR), using hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant spherical HA-siCD98/CUR-NPs are featured by a desirable particle size (∼246 nm) and slightly negative zeta potential (∼-14 mV). The NPs functionalized with HA are able to guide the co-delivery of drugs to the targeted cells related to UC therapy (colonic epithelial cells and macrophages). Compared to either siCD98- or CUR-based monotherapy, co-delivery of siCD98 and CUR by HA-functionalized NPs can exert combinational effects against UC by protecting the mucosal layer and alleviating inflammation both in vitro and in vivo. This study shows the promising capability of the co-delivered siCD98 and CUR for boosting the conventional monotherapy via this novel nanotherapeutic agent, which offers a structurally simple platform for orally administered delivery of drugs to target cells in UC therapy.
Collapse
|
|
35
|
Zhang M, Viennois E, Prasad M, Zhang Y, Wang L, Zhang Z, Han MK, Xiao B, Xu C, Srinivasan S, Merlin D. Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer. Biomaterials 2016; 101:321-40. [PMID: 27318094 PMCID: PMC4921206 DOI: 10.1016/j.biomaterials.2016.06.018] [Citation(s) in RCA: 542] [Impact Index Per Article: 60.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Revised: 06/02/2016] [Accepted: 06/07/2016] [Indexed: 12/11/2022]
Abstract
There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. In this study, we characterized a specific population of nanoparticles derived from edible ginger (GDNPs 2) and demonstrated their efficient colon targeting following oral administration. GDNPs 2 had an average size of ∼230 nm and exhibited a negative zeta potential. These nanoparticles contained high levels of lipids, a few proteins, ∼125 microRNAs (miRNAs), and large amounts of ginger bioactive constituents (6-gingerol and 6-shogaol). We also demonstrated that GDNPs 2 were mainly taken up by intestinal epithelial cells (IECs) and macrophages, and were nontoxic. Using different mouse colitis models, we showed that GDNPs 2 reduced acute colitis, enhanced intestinal repair, and prevented chronic colitis and colitis-associated cancer (CAC). 2D-DIGE/MS analyses further identified molecular target candidates of GDNPs 2 involved in these mouse models. Oral administration of GDNPs 2 increased the survival and proliferation of IECs and reduced the pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), and increased the anti-inflammatory cytokines (IL-10 and IL-22) in colitis models, suggesting that GDNPs 2 has the potential to attenuate damaging factors while promoting the healing effect. In conclusion, GDNPs 2, nanoparticles derived from edible ginger, represent a novel, natural delivery mechanism for improving IBD prevention and treatment with an added benefit of overcoming limitations such as potential toxicity and limited production scale that are common with synthetic nanoparticles.
Collapse
Affiliation(s)
- Mingzhen Zhang
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
| | - Emilie Viennois
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA
| | - Meena Prasad
- Veterans Affairs Medical Center, Decatur, GA, USA; Emory University, Department of Medicine, USA
| | - Yunchen Zhang
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA
| | - Lixin Wang
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA; Veterans Affairs Medical Center, Decatur, GA, USA
| | - Zhan Zhang
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA
| | - Moon Kwon Han
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA
| | - Bo Xiao
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA; Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing, 400715, PR China
| | - Changlong Xu
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA; The 2nd Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, PR China
| | - Shanthi Srinivasan
- Veterans Affairs Medical Center, Decatur, GA, USA; Emory University, Department of Medicine, USA
| | - Didier Merlin
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA; Veterans Affairs Medical Center, Decatur, GA, USA
| |
Collapse
|
|
36
|
Safdari Y, Ahmadzadeh V, Khalili M, Jaliani HZ, Zarei V, Erfani-Moghadam V. Use of single chain antibody derivatives for targeted drug delivery. Mol Med 2016; 22:258-270. [PMID: 27249008 DOI: 10.2119/molmed.2016.00043] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Accepted: 04/22/2016] [Indexed: 01/01/2023] Open
Abstract
Single chain antibodies (scFvs), which contain only the variable domains of full-length antibodies, are relatively small molecules that can be used for selective drug delivery. In this review, we display how scFv antibodies help improve the specificity and efficiency of drugs. Small interfering RNA (siRNA) delivery using scFv-drug fusion peptides, siRNA delivery using scFv-conjugated nanoparticles, targeted delivery using scFv-viral peptide- fusion proteins, use of scFv in fusion with cell penetrating peptides for effective targeted drug delivery, scFv-mediated targeted delivery of inorganic nanoparticles, scFv-mediated increase of tumor killing activity of granulocytes, use of scFv for tumor imaging, site-directed conjugation of scFv molecules to drug carrier systems, use of scFv to relieve pain, use of scFv for increasing drug loading efficiency are among the topics that are discussed here.
Collapse
Affiliation(s)
- Yaghoub Safdari
- Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.,Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| | - Vahideh Ahmadzadeh
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Masoumeh Khalili
- Golestan Research Center of Gastroenterology and Hepatology (GRCGH), Golestan University of Medical Sciences, Gorgan, Iran
| | - Hossein Zarei Jaliani
- Department of Advanced Medical Sciences and Technologies, School of Paramedicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Vahid Zarei
- Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran
| | - Vahid Erfani-Moghadam
- Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.,Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
| |
Collapse
|
|
37
|
Zhang M, Viennois E, Xu C, Merlin D. Plant derived edible nanoparticles as a new therapeutic approach against diseases. Tissue Barriers 2016; 4:e1134415. [PMID: 27358751 DOI: 10.1080/21688370.2015.1134415] [Citation(s) in RCA: 207] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2015] [Revised: 12/15/2015] [Accepted: 12/16/2015] [Indexed: 12/17/2022] Open
Abstract
In plant cells, nanoparticles containing miRNA, bioactive lipids and proteins serve as extracellular messengers to mediate cell-cell communication in a manner similar to the exosomes secreted by mammalian cells. Notably, such nanoparticles are edible. Moreover, given the proper origin and cargo, plant derived edible nanoparticles could function in interspecies communication and may serve as natural therapeutics against a variety of diseases. In addition, nanoparticles made of plant-derived lipids may be used to efficiently deliver specific drugs. Plant derived edible nanoparticles could be more easily scaled up for mass production, compared to synthetic nanoparticles. In this review, we discuss recent significant developments pertaining to plant derived edible nanoparticles and provide insight into the use of plants as a bio-renewable, sustainable, diversified platform for the production of therapeutic nanoparticles.
Collapse
Affiliation(s)
- Mingzhen Zhang
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA
| | - Emilie Viennois
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA
| | - Changlong Xu
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA; The 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Didier Merlin
- Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, USA; Atlanta Veterans Affairs Medical Center, Decatur, GA, USA
| |
Collapse
|
|
38
|
Youshia J, Lamprecht A. Size-dependent nanoparticulate drug delivery in inflammatory bowel diseases. Expert Opin Drug Deliv 2015; 13:281-94. [PMID: 26637060 DOI: 10.1517/17425247.2016.1114604] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is a chronic autoimmune disease, whose main forms are Crohn's disease and ulcerative colitis. The main treatment of IBD includes oral administration of anti-inflammatory or immunosuppressive agents enclosed in traditional dosage forms, intended to release the active ingredient in the large intestine. However, most of them have been designed based on the physiology of healthy colon, which differs distinctly from conditions met in IBD patients risking adverse effects and patient intolerance. The use of nanoparticles as a drug carrier for treatment of IBD is a promising approach that is capable of solving this problem. Previous studies have shown a size-dependent behavior, where reducing the particle size, increases the targeting efficacy and the residence time compared to healthy controls. AREAS COVERED This review covers the utilization of nanoparticles as drug delivery carriers for treating IBD. They can reach the inflamed colonic sites either by endothelial or epithelial delivery employing passive and active targeting strategies. The effect of particle size is analyzed in detail while elucidating other essential parameters such as the particle surface properties. EXPERT OPINION One of the most important advantages of nanoparticles is their passive targeting to the inflamed colonic tissues due to their size. Recent findings underline that this size-dependent bioadhesion behavior can be further enhanced by selecting smart surface properties to help in penetrating the mucus and reach the inflamed sites.
Collapse
Affiliation(s)
- John Youshia
- a Department of Pharmaceutics , Institute of Pharmacy, University of Bonn , Bonn , Germany.,b Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Ain Shams University , Cairo , Egypt
| | - Alf Lamprecht
- a Department of Pharmaceutics , Institute of Pharmacy, University of Bonn , Bonn , Germany.,c Laboratory of Pharmaceutical Engineering, EA 4267 , University of Franche-Comté , Besançon , France
| |
Collapse
|
|
39
|
Xiao B, Han MK, Viennois E, Wang L, Zhang M, Si X, Merlin D. Hyaluronic acid-functionalized polymeric nanoparticles for colon cancer-targeted combination chemotherapy. NANOSCALE 2015; 7:17745-55. [PMID: 26455329 PMCID: PMC4618760 DOI: 10.1039/c5nr04831a] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/27/2023]
Abstract
Nanoparticle (NP)-based combination chemotherapy has been proposed as an effective strategy for achieving synergistic effects and targeted drug delivery for colon cancer therapy. Here, we fabricated a series of hyaluronic acid (HA)-functionalized camptothecin (CPT)/curcumin (CUR)-loaded polymeric NPs (HA-CPT/CUR-NPs) with various weight ratios of CPT to CUR (1 : 1, 2 : 1 and 4 : 1). The resultant spherical HA-CPT/CUR-NPs had a desirable particle size (around 289 nm), relative narrow size distribution, and slightly negative zeta potential. These NPs exhibited a simultaneous sustained release profile for both drugs throughout the time frame examined. Subsequent cellular uptake experiments demonstrated that the introduction of HA to the NP surface endowed NPs with colon cancer-targeting capability and markedly increased cellular uptake efficiency compared with chitosan-coated NPs. Importantly, the combined delivery of CPT and CUR in one HA-functionalized NP exerted strong synergistic effects. HA-CPT/CUR-NP (1 : 1) showed the highest antitumor activity among the three HA-CPT/CUR-NPs, resulting in an extremely low combination index. Collectively, our findings indicate that this HA-CPT/CUR-NP can be exploited as an efficient formulation for colon cancer-targeted combination chemotherapy.
Collapse
Affiliation(s)
- Bo Xiao
- Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing, 400715, P. R. China
- Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Georgia State University, Atlanta, 30302, USA
| | - Moon Kwon Han
- Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Georgia State University, Atlanta, 30302, USA
| | - Emilie Viennois
- Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Georgia State University, Atlanta, 30302, USA
- Atlanta Veterans Affairs Medical Center, Decatur, 30033, USA
| | - Lixin Wang
- Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Georgia State University, Atlanta, 30302, USA
- Atlanta Veterans Affairs Medical Center, Decatur, 30033, USA
| | - Mingzhen Zhang
- Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Georgia State University, Atlanta, 30302, USA
| | - Xiaoying Si
- Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing, 400715, P. R. China
| | - Didier Merlin
- Center for Diagnostics and Therapeutics, Institute for Biomedical Science, Georgia State University, Atlanta, 30302, USA
- Atlanta Veterans Affairs Medical Center, Decatur, 30033, USA
| |
Collapse
|
|
40
|
Xiao B, Si X, Zhang M, Merlin D. Oral administration of pH-sensitive curcumin-loaded microparticles for ulcerative colitis therapy. Colloids Surf B Biointerfaces 2015; 135:379-385. [PMID: 26275840 DOI: 10.1016/j.colsurfb.2015.07.081] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Revised: 07/24/2015] [Accepted: 07/30/2015] [Indexed: 02/07/2023]
Abstract
Oral colon-specific drug delivery is of great interest for ulcerative colitis (UC) therapy. Here, an emulsion-solvent evaporation method was used to fabricate microparticles (MPs) with pH-sensitive Eudragit S100 (ERS100) and poly(lactide-co-glycolide) (PLGA), and the MPs were loaded with curcumin (an efficient anti-inflammatory agent). The resultant spherical MPs had a desirable particle size ranging from 1.52 to 1.91 μm. Their loading efficiency could be regulated by changing the weight ratios of ERS100 and PLGA, with some MPs exhibiting loading efficiencies over 80%. It was observed that the fast release of curcumin from MPs in buffers (pH 1.2 and 6.8) could be significantly decreased by increasing the PLGA content. ERS100/PLGA MPs with a weight ratio of 1:2 (MPs-4) were able to maintain sustained release of curcumin, releasing ∼ 48% of the initial drug load at pH 7.2-7.4 during a 20 h-incubation. Most importantly, in vivo experiments revealed that orally administered MPs-4 had a superior therapeutic efficiency in alleviating colitis in a UC mouse model, compared to curcumin. Collectively, our one-step-fabricated curcumin-loaded MPs have the properties of pH-sensitivity, controlled drug release and colon targeting, and thus, may hold promise as a readily scalable drug carrier for the efficient clinical treatment of UC.
Collapse
Affiliation(s)
- Bo Xiao
- Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing 400715, PR China; Center for Diagnostics and Therapeutics, Institute for Biomedical Sciences, Georgia State University, Atlanta 30302, USA.
| | - Xiaoying Si
- Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing 400715, PR China
| | - Mingzhen Zhang
- Center for Diagnostics and Therapeutics, Institute for Biomedical Sciences, Georgia State University, Atlanta 30302, USA
| | - Didier Merlin
- Center for Diagnostics and Therapeutics, Institute for Biomedical Sciences, Georgia State University, Atlanta 30302, USA; Atlanta Veterans Affairs Medical Center, Decatur 30033, USA
| |
Collapse
|
|
41
|
Hua S, Marks E, Schneider JJ, Keely S. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 2015; 11:1117-32. [PMID: 25784453 DOI: 10.1016/j.nano.2015.02.018] [Citation(s) in RCA: 349] [Impact Index Per Article: 34.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Revised: 02/02/2015] [Accepted: 02/25/2015] [Indexed: 12/15/2022]
Abstract
UNLABELLED Colon targeted drug delivery is an active area of research for local diseases affecting the colon, as it improves the efficacy of therapeutics and enables localized treatment, which reduces systemic toxicity. Targeted delivery of therapeutics to the colon is particularly advantageous for the treatment of inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. Advances in oral drug delivery design have significantly improved the bioavailability of drugs to the colon; however in order for a drug to have therapeutic efficacy during disease, considerations must be made for the altered physiology of the gastrointestinal (GI) tract that is associated with GI inflammation. Nanotechnology has been used in oral dosage formulation design as strategies to further enhance uptake into diseased tissue within the colon. This review will describe some of the physiological challenges faced by orally administered delivery systems in IBD, the important developments in orally administered nano-delivery systems for colon targeting, and the future advances of this research. FROM THE CLINICAL EDITOR Inflammatory Bowel Disease (IBD) poses a significant problem for a large number of patients worldwide. Current medical therapy mostly aims at suppressing the active inflammatory episodes. In this review article, the authors described and discussed the various approaches current nano-delivery systems can offer in overcoming the limitations of conventional drug formulations.
Collapse
Affiliation(s)
- Susan Hua
- The School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia.
| | - Ellen Marks
- The School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia; Gastrointestinal Research Group, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| | - Jennifer J Schneider
- The School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia
| | - Simon Keely
- The School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, Australia; Gastrointestinal Research Group, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
| |
Collapse
|