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Fabrication of Polymer Micelles with Zwitterionic Shell and Biodegradable Core for Reductively Responsive Release of Doxorubicin

1
School of Chemical Engineering & Pharmaceutics, Henan University of Science & Technology, 263# Kaiyuan Road, Luoyang 471023, China
2
School of Medicine, Henan University of Science & Technology, 263# Kaiyuan Road, Luoyang 471023, China
*
Author to whom correspondence should be addressed.
Polymers 2019, 11(6), 1019; https://doi.org/10.3390/polym11061019
Received: 11 April 2019 / Revised: 27 May 2019 / Accepted: 6 June 2019 / Published: 9 June 2019
(This article belongs to the Special Issue Self-assembly of Block Copolymers)
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Abstract

To achieve a high stability in physiological environment and rapid intracellular drug release, a biodegradable zwitterionic triblock copolymer with a disulfide-linked poly-ε-caprolactone and polycarboxybetaine methacrylate (PCBMA-SS-PCL-SS-PCBMA) was prepared for micellar carrier to delivery doxorubicin (DOX) into tumor cells. PCBMA-SS-PCL-SS-PCBMA was obtained by following steps: i) introducing disulfide bonds through end-group modification of PCL diol with cystamine dihydrochloride; ii) preparing PCL-RAFT macromolecular chain transfer agent by EDC/NHS chemistry; iii) RAFT polymerization of zwitterionic monomer. Self-assembling from PCBMA-SS-PCL-SS-PCBMA, polymeric micelles had many advantages, such as ultra-low protein absorption in serum and obvious reduction-responsiveness in the presence of DTT. Furthermore, DOX-loaded micelles exhibited high stability upon centrifugation and lyophilization, a fast intracellular drug release and enhanced drug efficacy due to GSH-triggered PCBMA shell shedding and micellar reassembling. Thus, the polymeric micelles integrated several functions and properties could be prospectively utilized as valuable nanocarriers in cancer chemotherapeutics. View Full-Text
Keywords: poly-ε-caprolactone; polycarboxybetaine; triblock copolymer; disulfide-linker; anticancer drugs; release poly-ε-caprolactone; polycarboxybetaine; triblock copolymer; disulfide-linker; anticancer drugs; release
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Jiang, J.; Li, J.; Zhou, B.; Niu, C.; Wang, W.; Wu, W.; Liang, J. Fabrication of Polymer Micelles with Zwitterionic Shell and Biodegradable Core for Reductively Responsive Release of Doxorubicin. Polymers 2019, 11, 1019.

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