期刊
JOURNAL OF PHARMACY AND PHARMACOLOGY
卷 73, 期 10, 页码 1405-1417出版社
OXFORD UNIV PRESS
DOI: 10.1093/jpp/rgab096
关键词
reduction-responsive micelles; controlled release; chondroitin sulfate A; alpha-tocopherol succinate; doxorubicin
资金
- Jiangxi Provincial Natural Science Foundation [20192ACBL20032, 20202BABL206155]
- Jiangxi Provincial Scientific Research Fund of Education Department [GJJ180900, GJJ201820]
- Jiujiang ShuangBai-ShuangQian Talents Plan [8400842]
- Jiangxi Provincial Scientific Research Fund of Health Commission [20195632, 20204271]
The reduction-responsive CST micelles can enhance the efficacy of DOX at the tumor site and control drug release. These micelles can form self-assembled micelles, with DOX-containing CST micelles showing reduction-triggered drug release in the presence of reducing agents. Furthermore, D-CST exhibited stronger cytotoxicity against A549 and AGS cells.
Objectives The study was to construct reduction-responsive chondroitin sulfate A (CSA)-conjugated TOS (CST) micelles with disulfide bond linkage, which was used for controlled doxorubicin (DOX) release and improved drug efficacy in vivo. Methods CST and non-responsive CSA-conjugated TOS (CAT) were synthesized, and the chemical structure was confirmed by Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (H-1 NMR) spectroscopy, fluorescence spectrophotometer and dynamic light scattering. Antitumour drug DOX was physically encapsulated into CST and CSA by dialysis method. Cell uptake of DOX-based formulations was investigated by confocal laser scanning microscopy. In vitro cytotoxicity was studied in A549 and AGS cells. Furthermore, antitumour activity was evaluated in A549-bearing mice. Key findings CST and CAT can form self-assembled micelles, and have low value of critical micelle concentration. Notably, DOX-containing CST (D-CST) micelles demonstrated reduction-triggered drug release in glutathione-containing media. Further, reduction-responsive uptake of D-CST was observed in A549 cells. In addition, D-CST induced stronger cytotoxicity (P < 0.05) than DOX-loaded CAT (D-CAT) against A549 and AGS cells. Moreover, D-CST exhibited significantly stronger antitumour activity in A549-bearing nude mice than doxorubicin hydrochloride and D-CAT. Conclusions The reduction-responsive CST micelles enhanced the DOX effect at tumour site and controlled drug release.
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