Doxorubicin-loaded folate-mediated pH-responsive micelle based on Bletilla striata polysaccharide: Release mechanism, cellular uptake mechanism, distribution, pharmacokinetics, and antitumor effects.

International Journal of Biological Macromolecules
Guangyuan ZhangQingxiang Guan

Abstract

This study evaluated the potential of folate (FA)-mediated and stearic acid (SA) modified Bletilla striata polysaccharide (FA-BSP-SA) copolymer as the vehicle for targeted delivery of anticancer drugs to tumor tissues and enhanced antitumor efficacy. The critical aggregation concentration, morphology, particle size, and zeta potential of micelles were increased with the reduction of pH values. The complex between doxorubicin (Dox) hydrochloride and sodium cholate via electrostatic interaction was fabricated and then directly encapsulated into FA-BSP-SA micelles. Dox in micelles existed in the status of amorphism. The Dox/FA-BSP-SA micelles demonstrated pH-responsive release behavior under the combination of diffusion and erosion mechanism. They could clearly strengthen the cellular uptake of Dox and inhibit the proliferation and the migration of tumor cells compared with the Dox/BSP-SA micelles and the free Dox. The Dox/FA-BSP-SA micelles were further delivered to lysosomes, mainly due to clathrin-mediated endocytosis. The FA-BSP-SA micelles distinctly improved the absolute bioavailability of Dox compared with the free Dox and the Dox/BSP-SA micelles (p < 0.01) and prolong the mean residence time. The Dox/FA-BSP-SA micelles sig...Continue Reading

Citations

Feb 6, 2021·Polymers·Leonard Ionut Atanase
Jul 17, 2021·International Journal of Biological Macromolecules·Dong Yu-HaoLiu Rui-Hai

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