Thermosensitive and Biodegradable Polymer Hydrogels

Synthesis of a thermosensitive, biodegradable hydrogel consisting of blocks of poly(ethylene oxide) and poly(L-lactic acid) was carried out (4). Aqueous solutions of these copolymers exhibited temperature-dependent reversible gel-sol transitions. The hydrogel can be loaded with bioactive molecules in an aqueous phase at an elevated temperature (around 45°C), where they form a solution. In this form, the polymer is injectable. On subcutaneous injection and subsequent rapid cooling to body temperature, the loaded copolymer forms a gel that can act as a sustained release matrix for drugs (4). 

In the next series of studies, Jeong et al. found compositions of HPL/HPB balanced triblock copolymers, PEG-PLGA-PEG, that exhibit sol-to-gel (lower transition) and gel-to-sol (upper transition) transitions as temperature mono-tonically increases (27). The lower transition is important for drug delivery application because the solution both flows freely at room temperature and becomes a gel at body 

This ABA-type triblock copolymer was used as a drug release depot for continuous release of hiunan insulin and of glucagons-like peptide-1 (GLP-1). The observation of both reduced initial burst and a constant release of hmnan insulin from ReGel in vitro is due to the domain structure of the gel and to the modification of the association states of insulin by zinc. Animal studies using SD rats were performed to verify the release profile of insuhn from this ABA block copolymer hydrogel. ReGel formrdation maintained insulin release for up to 15 days, which could allow diabetic patients to reduce the number of insulin injections to two per month for basal insulin requirements (31). 

BIODEGRADABLE MICROSPHERES BASED ON THE THERMOSENSITIVE PROPERTY OF PLCA-PEC-PLCA 

However, there are drawbacks observed in protein-loaded microspheres. The protein release kinetics exhibits an initial fast release followed by a slow release, resulting in an incomplete protein release despite significant degradation of microspheres (36). The very slow release kinetics was attributed to the protein aggregation and nonspecific adsorption within the microspheres. It was found that the protein 

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