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Polymers 2015, 7(11), 2245-2258; doi:10.3390/polym7111511

Bioreducible Micelles Self-Assembled from Poly(ethylene glycol)-Cholesteryl Conjugate As a Drug Delivery Platform

Division of Nano and Energy Convergence Research, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 711-873, Korea
These authors contributed equally to this work.
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Author to whom correspondence should be addressed.
Academic Editor: Michael K.C. Tam
Received: 22 September 2015 / Revised: 27 October 2015 / Accepted: 30 October 2015 / Published: 6 November 2015
(This article belongs to the Special Issue Stimuli-Responsive Polymers and Colloids)
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Abstract

The ability of polymeric micelles to self-assemble into nanosized particles has created interest in their application as potential anticancer drug delivery systems. A poly(ethylene glycol)-cholesteryl conjugate (Chol-ss-PEG-ss-Chol) connected by cleavable disulfide linkages was synthesized and used as a nanocarrier for in vitro release of doxorubicin (DOX). Owing to its amphiphilic structure, Chol-ss-PEG-ss-Chol was able to self-assemble into micelles with an average diameter 18.6 nm in aqueous solution. The micelles formed large aggregates due to the shedding of the PEG shell through cleavage of disulfide bonds in a reductive environment. The in vitro release studies revealed that Chol-ss-PEG-ss-Chol micelles released 80% and approximately 9% of the encapsulated DOX within 6 h under reductive and non-reductive conditions, respectively. The glutathione (GSH)-mediated intracellular drug delivery was investigated in a KB cell line. The cytotoxicity of DOX-loaded micelles indicated a higher cellular anti-proliferative effect against GSH-pretreated than untreated KB cells. Furthermore, confocal laser scanning microscopy (CLSM) measurement demonstrated that Chol-ss-PEG-ss-Chol micelles exhibited faster drug release in GSH-pretreated KB cells than untreated KB cells. These results suggest the potential usefulness of disulfide-based polymeric micelles as controlled drug delivery carriers. View Full-Text
Keywords: polymeric micelles; drug delivery system; biocompatible; disulfide-thiol exchange; stimulus-sensitive polymers polymeric micelles; drug delivery system; biocompatible; disulfide-thiol exchange; stimulus-sensitive polymers
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Baek, C.; Ha, T.-L.; Kim, E.; Jeong, S.W.; Lee, S.G.; Lee, S.J.; Kim, H.-C. Bioreducible Micelles Self-Assembled from Poly(ethylene glycol)-Cholesteryl Conjugate As a Drug Delivery Platform. Polymers 2015, 7, 2245-2258.

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