Dataset Information

Thermogelling, ABC Triblock Copolymer Platform for Resorbable Hydrogels with Tunable, Degradation-Mediated Drug Release.

ABSTRACT: 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(?-caprolactone), and fast hydrolytically/enzymatically degradable poly(D,L-lactide-co-glycolide), forming the respective formulations PPS135-b-PDMA152-b-PNIPAAM225 (PDN), PCL85-b-PDMA150-b-PNIPAAM150 (CDN), and PLGA60-b-PDMA148-b-PNIPAAM152 (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.

SUBMITTER: Gupta MK

PROVIDER: S-EPMC6195316 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Thermogelling, ABC Triblock Copolymer Platform for Resorbable Hydrogels with Tunable, Degradation-Mediated Drug Release.

Gupta Mukesh K MK Martin John R JR Dollinger Bryan R BR Hattaway Madison E ME Duvall Craig L CL

Advanced functional materials 20171027 47

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 sulfi ...[more]

PMID: 30349427

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Project description:Polymerization-induced self-assembly (PISA) has been widely utilized as a powerful methodology for the preparation of various self-assembled AB diblock copolymer nano-objects in aqueous media. Moreover, it is well-documented that chain extension of AB diblock copolymer vesicles using a range of hydrophobic monomers via seeded RAFT aqueous emulsion polymerization produces framboidal ABC triblock copolymer vesicles with adjustable surface roughness owing to microphase separation between the two enthalpically incompatible hydrophobic blocks located within their membranes. However, the utilization of hydrophilic monomers for the chain extension of linear diblock copolymer vesicles has yet to be thoroughly explored; this omission is addressed for aqueous PISA formulations in the present study. Herein poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (G-H) vesicles were used as seeds for the RAFT aqueous dispersion polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA). Interestingly, this led to polymerization-induced disassembly (PIDA), with the initial precursor vesicles being converted into lower-order worms or spheres depending on the target mean degree of polymerization (DP) for the corona-forming POEGMA block. Moreover, construction of a pseudo-phase diagram revealed an unexpected copolymer concentration dependence for this PIDA formulation. Previously, we reported that PHPMA-based diblock copolymer nano-objects only exhibit thermoresponsive behavior over a relatively narrow range of compositions and DPs (see Warren et al., Macromolecules, 2018, 51, 8357-8371). However, introduction of the POEGMA coronal block produced thermoresponsive ABC triblock nano-objects even when the precursor G-H diblock copolymer vesicles proved to be thermally unresponsive. Thus, this new approach is expected to enable the rational design of new nano-objects with tunable composition, copolymer architectures and stimulus-responsive behavior.

Dataset Information

Thermogelling, ABC Triblock Copolymer Platform for Resorbable Hydrogels with Tunable, Degradation-Mediated Drug Release.

Publications

Thermogelling, ABC Triblock Copolymer Platform for Resorbable Hydrogels with Tunable, Degradation-Mediated Drug Release.

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