Decanoic acid-modified glycol chitosan hydrogels containing tightly adsorbed palmityl-acylated exendin-4 as a long-acting sustained-release anti-diabetic system

Lee, Changkyu; Choi, Ji Su; Kim, In-Soo; Byeon, Hyeong Jun; Kim, Tae Hyung; Oh, Kyung Taek; Lee, Eun Seong; Lee, Kang Choon; Youn, Yu Seok

doi:10.1016/j.actbio.2013.10.009

Cited by 20 publications

(10 citation statements)

References 30 publications

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“…Over the past decade, injectable polymeric hydrogels have been extensively investigated as promising carriers for sustained delivery of a variety of drugs due to their good biocompatibility, easy administration, and minimally invasive therapy. − In particular, injectable thermosensitive hydrogels exhibit free-flowing sols at room or low temperature yet turn into semisolid physical hydrogels with an increase of temperature. − Therefore, fragile therapeutic agents, such as protein, polypeptide or other small molecules, may be easily entrapped in the sol state at low temperature, and then the drug-loaded polymer solution spontaneously forms an in situ hydrogel at body temperature after injection into the body using a conventional syringe. Subsequently, the drugs could be released from the gel matrix in a sustained manner by drug diffusion or polymer degradation.…”

Section: Introductionmentioning

confidence: 99%

Injectable and Thermosensitive Hydrogel Containing Liraglutide as a Long-Acting Antidiabetic System

Chen

Luan

Shen

et al. 2016

ACS Appl. Mater. Interfaces

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Diabetes, a global epidemic, has become a serious threat to public health. The present study is aimed at constructing an injectable thermosensitive PEG-polyester hydrogel formulation of liraglutide (Lira), a "smart" antidiabetic polypeptide, in the long-acting treatment of type 2 diabetes mellitus. A total of three thermosensitive poly(ε-caprolactone-co-glycolic acid)-poly(ethylene glycol)-poly(ε-caprolactone-co-glycolic acid) (PCGA-PEG-PCGA) triblock copolymers with similar molecular weights but different ε-caprolactone-to-glycolide (CL-to-GA) ratios were synthesized. The polymer aqueous solutions exhibited free-flowing sols at room temperature and formed in situ hydrogels at body temperature. While the different bulk morphologies, stabilities of aqueous solutions, and the varying in vivo persistence time of hydrogels in ICR mice were found among the three copolymers, all of the Lira-loaded gel formulations exhibited a sustained drug release manner in vitro regardless of CL-to-GA ratios. The specimen with a powder form in the bulk state, a stable aqueous solution before heating, and an appropriate degradation rate in vivo was selected as the optimal carrier to evaluate the in vivo efficacy. A single injection of the optimal gel formulation showed a remarkable hypoglycemic efficacy up to 1 week in diabetic db/db mice. Furthermore, three successive administrations of this gel formulation within one month significantly lowered glycosylated hemoglobin and protected islets of db/db mice. As a result, a promising once-weekly delivery system of Lira was developed, which not only afforded long-term glycemic control but also significantly improved patient compliance.

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Section: Introductionmentioning

confidence: 99%

Injectable and Thermosensitive Hydrogel Containing Liraglutide as a Long-Acting Antidiabetic System

Chen

Luan

Shen

et al. 2016

ACS Appl. Mater. Interfaces

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“…Advancing the albumi-binding strategy, Lee et al combined the nanotechnology to further extend the plasma half-lives of exendin-4. In their study, decanoic acid-modified glycol chitosan (DA-GC) hydrogels containing palmitic acid-modified exendin-4(Ex4-C16) were prepared [69]. The Ex4-C16 containing DA-GC hydrogels (Ex4-C16 DA-GC) could slowly release the EX4-C16 for 21 days in vitro and, with s.c. administration in db/db diabetic mice, hypoglycemic effects were achieved for eight days.…”

Section: Non-covalent Albumin Bindingmentioning

confidence: 99%

Drug Delivery Strategies for Enhancing the Therapeutic Efficacy of Toxin-Derived Anti-Diabetic Peptides

Amatya

Park

Hwang

et al. 2020

Toxins

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Toxin peptides derived from the skin secretions of amphibians possess unique hypoglycemic activities. Many of these peptides share cationic and amphipathic structural similarities and appear to possess cell-penetrating abilities. The mechanism of their insulinotropic action is yet not elucidated, but they have shown great potential in regulating the blood glucose levels in animal models. Therefore, they have emerged as potential drug candidates as therapeutics for type 2 diabetes. Despite their anti-diabetic activity, there remain pharmaceutical challenges to be addressed for their clinical applications. Here, we present an overview of recent studies related to the toxin-derived anti-diabetic peptides derived from the skin secretions of amphibians. In the latter part, we introduce the bottleneck challenges for their delivery in vivo and general drug delivery strategies that may be applicable to extend their blood circulation time. We focus our research on the strategies that have been successfully applied to improve the plasma half-life of exendin-4, a clinically available toxin-derived anti-diabetic peptide drug.

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“…This indicates a growing need for treatments that provide both sustained release and targeted action [ 8 , 9 , 10 ]. In diabetes management, long-acting gels are crucial for the continuous and controlled delivery of medications to effectively regulate blood glucose levels, reflecting a trend towards enhancing patient convenience and treatment success [ 11 , 12 , 13 , 14 , 15 , 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Long-Acting Gel Formulations: Advancing Drug Delivery across Diverse Therapeutic Areas

Omidian,

Wilson

2024

Pharmaceuticals

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This multifaceted landscape of long-acting gels in diverse medical fields, aims to enhance therapeutic outcomes through localized treatment and controlled drug release. The objective involves advancements spanning cancer treatment, immunotherapy, diabetes management, neuroendocrine disorders, ophthalmic applications, contraception, HIV/AIDS treatment, chronic diseases, wound care, and antimicrobial treatments. It explores the potential of long-acting gels to offer sustained and extended drug release, targeted therapy, and innovative administration routes while addressing limitations such as scalability challenges and regulatory hurdles. Future directions focus on personalized therapies, biodegradability, combination therapies, interdisciplinary innovation, regulatory considerations, and patient-centric development. This comprehensive review highlights the pivotal role of long-acting gels in transforming therapeutic approaches and improving patient outcomes across various medical conditions.

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Decanoic acid-modified glycol chitosan hydrogels containing tightly adsorbed palmityl-acylated exendin-4 as a long-acting sustained-release anti-diabetic system

Cited by 20 publications

References 30 publications

Injectable and Thermosensitive Hydrogel Containing Liraglutide as a Long-Acting Antidiabetic System

Injectable and Thermosensitive Hydrogel Containing Liraglutide as a Long-Acting Antidiabetic System

Drug Delivery Strategies for Enhancing the Therapeutic Efficacy of Toxin-Derived Anti-Diabetic Peptides

Long-Acting Gel Formulations: Advancing Drug Delivery across Diverse Therapeutic Areas

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