Preparation and evaluation of reduction-responsive micelles based on disulfide-linked chondroitin sulfate A-tocopherol succinate for controlled antitumour drug release
| Autor: | Weidong Li, Qinglan Yuan, Lijia Meng, Xin Xie, Junzhi Li, Songjin Cai, Jingmou Yu, Ming He, Jian Ding |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lung Neoplasms
Polymers alpha-Tocopherol Mice Nude Pharmaceutical Science Case Report 02 engineering and technology 010402 general chemistry 01 natural sciences Micelle Drug Delivery Systems Stomach Neoplasms In vivo Cell Line Tumor Neoplasms medicine Animals Humans Doxorubicin Disulfides Cytotoxicity Micelles Pharmacology A549 cell Drug Carriers Mice Inbred BALB C Antibiotics Antineoplastic Chemistry Chondroitin Sulfates 021001 nanoscience & nanotechnology Xenograft Model Antitumor Assays Controlled release 0104 chemical sciences Drug Liberation A549 Cells Delayed-Action Preparations Critical micelle concentration Biophysics Doxorubicin Hydrochloride 0210 nano-technology human activities medicine.drug |
| Zdroj: | Case Reports in Nephrology |
| ISSN: | 2042-7158 0022-3573 |
| DOI: | 10.1093/jpp/rgab096 |
| Popis: | 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 (1H 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. |
| Databáze: | OpenAIRE |
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