Li Yan Qiu1, Rong Juan Wang, Cheng Zheng, Yi Jin, Le Qun Jin. 1. Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 388 Yu-Hang-Tang Road, Hangzhou, 310058, China. lyqiu@zju.edu.cn
Abstract
AIM: Delivery of doxorubicin could be achieved by a novel micellar system based on beta-cyclodextrin-centered star-shaped amphiphilic polymers (sPEL/CD). This study specifically explored the effect of polylactide segments in sPEL/CD on various micelle properties, such as the critical micelle concentration, size, drug loading, cytotoxicity and drug resistance reversing effect. METHOD: The sPEL/CD was synthesized by the arm-first method. The critical micelle concentrations of polymeric micelles were determined by fluorescence spectrophotometry using pyrene as a probe. The oil/water method was applied to prepare doxorubicin-loaded micelles. 3-(4,5-dimethylthi-azol-2-yl)-2,5-diphenyltetrazolium bromide, confocal laser-scanning microscopy and flow cytometry were used to examine cell cytotoxicity and cellular uptake of the doxorubicin-loaded micelles. Finally, rhodamine-123 cellular uptake was determined to evaluate the polymer action on MCF-7 and MCF-7/ADR cells. RESULTS: All polymers exhibited low cytotoxicity and their micelles had a desirable release-acceleration pH (pH 5.0) for cytoplasmic drug delivery. With the introduction of polylactide into the polymer, the micelle critical micelle concentration can be effectively decreased and the drug-loading content was enhanced. Most importantly, the drug resistance of MCF-7/ADR cells was significantly reversed via the interaction between polymer and Pgp. Therefore, this type of polymer has potential superiority for cancer therapy.
AIM: Delivery of doxorubicin could be achieved by a novel micellar system based on beta-cyclodextrin-centered star-shaped amphiphilic polymers (sPEL/CD). This study specifically explored the effect of polylactide segments in sPEL/CD on various micelle properties, such as the critical micelle concentration, size, drug loading, cytotoxicity and drug resistance reversing effect. METHOD: The sPEL/CD was synthesized by the arm-first method. The critical micelle concentrations of polymeric micelles were determined by fluorescence spectrophotometry using pyrene as a probe. The oil/water method was applied to prepare doxorubicin-loaded micelles. 3-(4,5-dimethylthi-azol-2-yl)-2,5-diphenyltetrazolium bromide, confocal laser-scanning microscopy and flow cytometry were used to examine cell cytotoxicity and cellular uptake of the doxorubicin-loaded micelles. Finally, rhodamine-123 cellular uptake was determined to evaluate the polymer action on MCF-7 and MCF-7/ADR cells. RESULTS: All polymers exhibited low cytotoxicity and their micelles had a desirable release-acceleration pH (pH 5.0) for cytoplasmic drug delivery. With the introduction of polylactide into the polymer, the micelle critical micelle concentration can be effectively decreased and the drug-loading content was enhanced. Most importantly, the drug resistance of MCF-7/ADR cells was significantly reversed via the interaction between polymer and Pgp. Therefore, this type of polymer has potential superiority for cancer therapy.
Authors: Yao Zhang; René Bartz; Gevorg Grigoryan; Michael Bryant; Jeff Aaronson; Stephen Beck; Nathalie Innocent; Lee Klein; William Procopio; Tom Tucker; Vasant Jadhav; David M Tellers; William F DeGrado Journal: ACS Chem Biol Date: 2015-01-28 Impact factor: 5.100
Authors: Olga A Mostovaya; Vladimir V Gorbachuk; Pavel L Padnya; Alena A Vavilova; Gennady A Evtugyn; Ivan I Stoikov Journal: Front Chem Date: 2019-08-02 Impact factor: 5.221