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Thermogelling, ABC Triblock Copolymer Platform for Resorbable Hydrogels with Tunable, Degradation‐Mediated Drug Release
Author(s) -
Gupta Mukesh K.,
Martin John R.,
Dollinger Bryan R.,
Hattaway Madison E.,
Duvall Craig L.
Publication year - 2017
Publication title -
advanced functional materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.069
H-Index - 322
eISSN - 1616-3028
pISSN - 1616-301X
DOI - 10.1002/adfm.201704107
Subject(s) - self healing hydrogels , copolymer , materials science , micelle , drug delivery , polymer , polymer chemistry , hydrolysis , aqueous solution , chemical engineering , lower critical solution temperature , organic chemistry , chemistry , nanotechnology , composite material , engineering
Clinical application of injectable, thermoresponsive hydrogels is hindered by lack of degradability and controlled drug release. To overcome these challenges, a family of thermoresponsive, ABC triblock polymer‐based hydrogels has been engineered to degrade and release drug cargo through either oxidative or hydrolytic/enzymatic mechanisms dictated by the “A” block composition. Three ABC triblock copolymers are synthesized with varying “A” blocks, including oxidation‐sensitive poly(propylene sulfide), slow hydrolytically/enzymatically degradable poly(ε‐caprolactone), and fast hydrolytically/enzymatically degradable poly( d , l ‐lactide‐ co ‐glycolide), forming the respective formulations PPS 135 ‐ b ‐PDMA 152 ‐ b ‐PNIPAAM 225 (PDN), PCL 85 ‐ b ‐PDMA 150 ‐ b ‐PNIPAAM 150 (CDN), and PLGA 60 ‐ b ‐PDMA 148 ‐ b ‐PNIPAAM 152 (LGDN). For all three polymers, hydrophilic poly( N , N ‐dimethylacrylamide) and thermally responsive poly( N ‐isopropylacrylamide) comprise the “B” and “C” blocks, respectively. These copolymers form micelles in aqueous solutions at ambient temperature that can be preloaded with small molecule drugs. These solutions quickly transition into hydrogels upon heating to 37 °C, forming a supra‐assembly of physically crosslinked, drug‐loaded micelles. PDN hydrogels are selectively degraded under oxidative conditions while CDN and LGDN hydrogels are inert to oxidation but show differential rates of hydrolytic/enzymatic decomposition. All three hydrogels are cytocompatible in vitro and in vivo, and drug‐loaded hydrogels demonstrate differential release kinetics in vivo corresponding with their specific degradation mechanism. These collective data highlight the potential cell and drug delivery use of this tunable class of ABC triblock polymer thermogels.