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Synthesis of poly(ethylene glycol)-SS-poly(ε-caprolactone)-SS-poly(ethylene glycol) triblock copolymers via end-group conjugation and self-assembly for reductively responsive drug delivery |
Junbo LI1(), Junting JIANG1, Biyu ZHOU1, Chaohuang NIU1, Wendi WANG1, Wenlan WU2 |
1. School of Chemical Engineering and Pharmaceutics, Henan University of Science and Technology, Luoyang 471023, China 2. School of Medicine, Henan University of Science and Technology, Luoyang 471023, China |
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Abstract In this study, we describe a simple synthesis route to prepare triblock copolymers with disulfide-linkers, poly(ethylene glycol)-SS-poly(ε-caprolactone)-SS-poly(ethylene glycol) (PEG-SS-PCL-SS-PEG) for application in the reductively responsive release of doxorubicin (DOX). To synthesize PEG-SS-PCL-SS-PEG, two end-groups of PCL-diol were first modified with cystamine to introduce disulfide bonds and subsequently conjugated with PEG-NHS via carbodiimide chemistry. PEG-SS-PCL-SS-PEG fabricated into polymeric micelles with stable structure and different nanoscale sizes via adjusting the PCL chain length, showing obvious reductive responsiveness and fast drug release of encapsulated DOX in the presence of glutathione (GSH). Moreover, DOX-loaded PEG-SS-PCL-SS-PEG micelles exhibited higher therapeutic efficacy than reduction-insensitive PEG-b-PCL micelles in vitro. Thus, end-groups conjugation is a simple and straightforward strategy to introduce intelligent responsiveness in biocompatible block copolymers and improve their therapeutic efficacy.
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Keywords
poly-ε-caprolactone
poly(ethylene glycol)
block copolymer
reductive responsiveness
drug
release
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Corresponding Author(s):
Junbo LI
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Online First Date: 07 November 2019
Issue Date: 04 December 2019
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