Accelerated wound healing by injectable star poly(ethylene glycol)-b-poly(propylene sulfide) scaffolds loaded with poorly water-soluble drugs.

TitleAccelerated wound healing by injectable star poly(ethylene glycol)-b-poly(propylene sulfide) scaffolds loaded with poorly water-soluble drugs.
Publication TypeJournal Article
Year of Publication2018
AuthorsS Zhu, S Li, H Escuin-Ordinas, R Dimatteo, W Xi, A Ribas, and T Segura
JournalJournal of Controlled Release : Official Journal of the Controlled Release Society
Volume282
Start Page156
Pagination156 - 165
Date Published07/2018
Abstract

Injectable hydrogel matrices take the shape of a wound cavity and serve as scaffold for tissue repair and regeneration. Yet these materials are generally hydrophilic, limiting the incorporation of poorly water soluble, hydrophobic drugs. Here we show this shortcoming is circumvented through a star-shaped amphiphilic block copolymer comprising poly(ethylene glycol) and poly (propylene sulfide). This star-shaped amphiphilic polymer self-assembles in an aqueous medium into a physically stable hydrogel and effectively dissolves hydrophobic molecules delivering them at therapeutic doses. The self assembled hydrogel is a robust three-dimensional scaffold in vivo effectively promoting cellular infiltration, reducing inflammation, and wound clsoure. When combined with a hydrophobic BRAF inhibitor that promotes paradoxical mitogen-activated protein kinase (MAPK) activation in keratinocytes and wound closure, our self assembled scaffold supported dermal wound closure at a reduced drug dosage compared to administering the drug in dimethyl sulfoxide (DMSO) without a polymeric matrix. This family of star-shaped amphiphilic polymers delivers poorly water soluble active agents at a fraction of generally required dosage for efficacy and supports three-dimensional cell growth at tissue wounds, showing great promise for novel uses of hydrophobic drugs in tissue repair applications.

DOI10.1016/j.jconrel.2018.05.006
Short TitleJournal of Controlled Release : Official Journal of the Controlled Release Society