Preparation and characterization of glutathione-responsive polymeric micelles functionalized with core cross-linked disulfide linkage for curcumin delivery

Conventional self-assembled polymeric micelles typically lose their loaded drugs after systemic administration. To resolve this issue, the aim of the present study was to develop a novel polymer, methoxy-poly (ethylene glycol)-block-poly ( d , l -lactic acid) grafted with four lipoic acids (mPEG-PLA...

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Bibliographic Details
Published in:Journal of polymer research 2019-05, Vol.26 (5), p.1-12, Article 103
Main Authors: Chen, Dan, Gong, Feirong, Han, Xiaoxiong, Chi, Lili, Sun, Jing, Shen, Yaling
Format: Article
Language:English
Subjects:
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Crosslinking
Drug delivery systems
Ethylene glycol
Glutathione
Industrial Chemistry/Chemical Engineering
Lactic acid
Liquid chromatography
Micelles
MPEG encoders
Original Paper
Orthogonality
Polymer Sciences
Self-assembly
Stability
Toxicity
Video compression
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Summary:Conventional self-assembled polymeric micelles typically lose their loaded drugs after systemic administration. To resolve this issue, the aim of the present study was to develop a novel polymer, methoxy-poly (ethylene glycol)-block-poly ( d , l -lactic acid) grafted with four lipoic acids (mPEG-PLA-(LA) 4 ), to prepare curcumin-loaded core cross-linked polymeric micelles (CCM). Nitrogen and alkalescent buffer (pH 8.5) were beneficial for cross-linking, and the cross-linking was nearly complete within 30 min. The micelle preparation parameters were optimized through both a single-factor experiment and orthogonality test. The choice of cryoprotector had the most important effect on micelle solution reconstruction and almost challenged our perceptions about cryoprotector. In addition the drug loading capacity greatly affected the stability of micelles. Moreover, a method for determining the cross-linking density was established, and the result of gel permeation chromatography indirectly demonstrated that dozens of polymers had successfully formed CCM. The CCM significantly enhanced stability under non-reductive conditions and could be reversibly broken in a reductive environment. Curcumin-loaded CCM also showed glutathione-response cytotoxicity to cancer cells. Overall, this fundamental study suggests CCM as a potential carrier for achieving improved controlled drug delivery.
ISSN:1022-9760
1572-8935
DOI:10.1007/s10965-019-1768-7