Development of polyvinylpyrrolidone/paclitaxel self-assemblies for breast cancer

作     者：Pallabita Chowdhury Prashanth K.B.Nagesh Sheema Khan Bilal B.Hafeez Subhash C.Chauhan Meena Jaggi Murali M.Yallapu 

作者机构：Department of Pharmaceutical Sciences and Center for Cancer ResearchUniversity of Tennessee Health Science Center 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2018年第8卷第4期

页      面：602-614页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1001[医学-基础医学(可授医学、理学学位)] 100602[医学-中西医结合临床] 10[医学] 

基　　金：performed under National Institute of Health/National Cancer Center's Career Development Award K22 CA174841,R15 CA 213232 CORNET-UTHSC,Start-up by the College of Pharmacy,UTHSC to Murali M.Yallapu gratefully acknowledge the National Institutes of Health Research Project Grant Program (R01 CA210192,R01 CA206069,and CA204552) to Subhash C.Chauhan UTHSC-College of Pharmacy-Dean's Seed Grant support to Murali M.Yallapu,Meena Jaggi and Subhash C.Chauhan 

主　　题：Drug delivery Nanoparticles Self-assemblies Polymer Cancer therapeutics Breast cancer 

摘      要：The goal of this investigation was to develop and demonstrate a polymer/paclitaxel selfassembly(PTX-SA) formulation. Polymer/PTX-SAs were screened based on smaller size of formulation using dynamic light scattering analysis. Additionally, fluorescence microscopy and flow cytometry studies exhibited that polyvinylpyrrolidone(PVP)-based PTX-SAs(PVP/PTX-SAs) had superior cellular internalization capability in MCF7 and MDA-MB-231 breast cancer cells. The optimized PVP/PTXSAs exhibited less toxicity to human red blood cells indicating a suitable formulation for reducing systemic toxicity. The formation of PVP and PTX self-assemblies was confirmed using fluorescence quenching and transmission electron microscopy which indicated that the PVP/PTX-SAs were spherical in shape with an average size range of 53.81 nm as detected by transmission electron microscopy(TEM).FTIR spectral analysis demonstrates incorporation of polymer and paclitaxel functional groups in PVP/PTX-SAs. Both proliferation(MTS) and clonogenic(colony formation) assays were used to validate superior anticancer activity of PVP/PTX-SAs in breast cancer cells over paclitaxel. Such superior anticancer activity was also demonstrated by downregulation of the expression of pro-survival protein(Bcl-x L), upregulation of apoptosis-associated proteins(Bid, Bax, cleaved caspase 7, and cleaved PARP)and β-tubulin stabilization. These results support the hypothesis that PVP/PTX-SAs improved paclitaxel delivery to cancer cells.