Liquid degradable poly(trimethylene-carbonate-co-5-hydroxy-trimethylene carbonate): an injectable drug delivery vehicle for acid-sensitive drugs.

07:00 EST 13th February 2020 | BioPortfolio

Summary of "Liquid degradable poly(trimethylene-carbonate-co-5-hydroxy-trimethylene carbonate): an injectable drug delivery vehicle for acid-sensitive drugs."

Liquid injectable hydrophobic polymers have advantages as degradable drug delivery vehicles; however, polymers examined for this purpose to date form acidic degradation products that may damage acid-sensitive drugs. Herein we report on a new viscous liquid copolymer, poly(trimethylene carbonate-co-5-hydroxy-trimethylene carbonate) that degrades through intramolecular cyclization in mild alkaline environments, producing glycerol, carbon dioxide, and water-soluble trimethylene carbonate. Copolymer degradation durations from weeks to months were obtained with 5-hydroxy-trimethylene carbonate (HTMC) content of the copolymer having the greatest impact on degradation rate, with copolymers possessing higher HTMC content degrading fastest. The degradation products of the copolymers were non-cytotoxic towards 3T3 fibroblasts and RAW 264.7 macrophages. These copolymers can be injected manually through standard gauge needles and, importantly, during in vitro degradation, the microenvironmental pH within the copolymer remained near neutral. Complete and sustained release of the acid-sensitive protein vascular endothelial growth factor was achieved, with the protein remaining highly bioactive throughout the release period. These copolymers represent a promising formulation approach for local and sustained release of acid sensitive drugs.


Journal Details

This article was published in the following journal.

Name: Molecular pharmaceutics
ISSN: 1543-8392


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