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A long-acting formulation of a polypeptide drug exenatide in treatment of diabetes using an injectable block copolymer hydrogel.

Abstract：

:This study is aimed to develop a long-acting injectable formulation in treatment of type II diabetes. A glucoregulatory polypeptide, exenatide (EXT), was chosen as the model drug, and an aqueous block copolymer system with a sol-gel transition upon the increase of temperature was selected as the delivery matrix of EXT. The thermoreversible hydrogel composed of poly(lactic acid-co-glycolic acid)-poly(ethylene glycol)-poly(lactic acid-co-glycolic acid) (PLGA-PEG-PLGA) triblock copolymers was found to slower the degradation of the polypeptide to a large extent. However, the initial formulation in this study exhibited a significant drug burst effect, which is a common problem to load a hydrophilic small or medium-size polypeptide into a hydrogel. Zinc acetate was then introduced to slow down the EXT release by formation of insoluble Zn-EXT complexes in the thermogel matrix. Yet an incomplete release became another crucial problem, which is also common for peptide and protein delivery. The synergistic effect of three excipients (zinc acetate, PEG, and sucrose) under an appropriate condition overcame these two problems simultaneously, and the sustained release of drug lasted for 1 week. In vivo experiments via mice oral glucose tolerance tests demonstrated an improved glucose tolerance for 1 week after a single subcutaneous injection of the optimal EXT formulation. As a result, a formulation of antidiabetic drugs was set up, and meanwhile a strategy using synergistic excipients to adjust release profiles of peptides from hydrogels was put forward.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Li K,Yu L,Liu X,Chen C,Chen Q,Ding J

doi

10.1016/j.biomaterials.2013.01.013

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

2834-42

issue

11

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(13)00021-5

journal_volume

34

pub_type

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