pH-temperature Responsive Hydrogel-Mediated Delivery of Exendin-4 Encapsulated Chitosan Nanospheres for Sustained Therapeutic Efficacy in Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus (T2D) is a chronic, obesity-related, and inflammatory disorder characterize by insulin resistance, inadequate insulin secretion, hyperglycemia, and excessive glucagon secretion. Exendin-4 (EX), a clinically established antidiabetic medication that acts as a glucagon-like pep...

Full description

Saved in:
Bibliographic Details
Published in:Macromolecular bioscience 2023-11, Vol.23 (11), p.e2300221-e2300221
Main Authors: Trinh, Thuy An, Le, Thai Minh Duy, Nguyen, Hien Thi-Thanh, Nguyen, Thanh Loc, Kim, Jaeyun, Huynh, Dai Phu, Lee, Doo Sung
Format: Article
Language:English
Subjects:
Biocompatibility
Chitosan
Copolymers
Diabetes
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Electrostatic properties
Glucagon
Hunger
Hydrogels
Hyperglycemia
Inflammatory diseases
Injection
Insulin
Insulin resistance
Insulin secretion
Micelles
Nanospheres
pH effects
Secretion
Sol-gel processes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Type 2 Diabetes Mellitus (T2D) is a chronic, obesity-related, and inflammatory disorder characterize by insulin resistance, inadequate insulin secretion, hyperglycemia, and excessive glucagon secretion. Exendin-4 (EX), a clinically established antidiabetic medication that acts as a glucagon-like peptide-1 receptor agonist, is effective in lowering glucose levels and stimulating insulin secretion while significantly reducing hunger. However, the requirement for multiple daily injections due to EX's short half-life is a significant limitation in its clinical application, leading to high treatment costs and patient inconvenience. To address this issue, an injectable hydrogel system is developed that can provide sustained EX release at the injection site, reducing the need for daily injections. In this study, the electrospray technique is examine to form EX@CS nanospheres by electrostatic interaction between cationic chitosan (CS) and negatively charged EX. These nanospheres are uniformly dispersed in a pH-temperature responsive pentablock copolymer, which forms micelles and undergoes sol-to-gel transition at physiological conditions. Following injection, the hydrogel gradually degraded, exhibiting excellent biocompatibility. The EX@CS nanospheres are subsequently released, maintaining therapeutic levels for over 72 h compared to free EX solution. The findings demonstrate that the pH-temperature responsive hydrogel system containing EX@CS nanospheres can be a promising platform for the treatment of T2D.
ISSN:1616-5187
1616-5195
DOI:10.1002/mabi.202300221