Development of polyvinylpyrrolidone/paclitaxel self-assemblies for breast cancer

Authors

Pallabita Chowdhury, University of Tennessee Health Science Center
Prashanth K.B. Nagesh, The University of Texas Rio Grande Valley
Sheema Khan, The University of Texas Rio Grande Valley
Bilal B. Hafeez, The University of Texas Rio Grande ValleyFollow
Subhash C. Chauhan, The University of Texas Rio Grande ValleyFollow
Meena Jaggi, The University of Texas Rio Grande ValleyFollow
Murali M. Yallapu, The University of Texas Rio Grande ValleyFollow

Document Type

Article

Publication Date

2018

Abstract

The goal of this investigation was to develop and demonstrate a polymer/paclitaxel self-assembly (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/PTX-SAs 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-xL), 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.

Comments

Copyright 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Recommended Citation

Chowdhury, P., Nagesh, P., Khan, S., Hafeez, B. B., Chauhan, S. C., Jaggi, M., & Yallapu, M. M. (2018). Development of polyvinylpyrrolidone/paclitaxel self-assemblies for breast cancer. Acta pharmaceutica Sinica. B, 8(4), 602–614. https://doi.org/10.1016/j.apsb.2017.10.004

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 International License.

Publication Title

Acta Pharmaceutica Sinica B

DOI

10.1016/j.apsb.2017.10.004

Academic Level

faculty

Mentor/PI Department

Immunology and Microbiology