Development of polyvinylpyrrolidone/paclitaxel self-assemblies for breast cancer

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.

Tannic Acid-Lung Fluid Assemblies Promote Interaction and Delivery of Drugs to Lung Cancer Cells

“…A semi-quantitative cellular uptake assay of TA-LF complexes was examined by flow cytometry and fluorescence microscopy methods. To allow cellular uptake quantification, TA-LF assemblies were labeled with coumarin-6 using our previously reported method [ 24 , 25 ]. The extent of dye internalized was used to track uptake of TA-LF self-assemblies into cells.…”

“…The drugs (gemcitabine, carboplatin, irinotecan) encapsulated in TA-LF formulations were prepared following our established protocol [ 24 ]. Their anti-cancer efficacies were evaluated using a colorimetric cell titer 96 aqueous one solution cell proliferation assay (MTS assay, Promega, Madison, WI, USA).…”

Immunogenicity of Polyethylene Glycol Based Nanomedicines: Mechanisms, Clinical Implications and Systematic Approach

“…This effect lacked interaction with the immune system. [ 130 ] In particular, Ishihara et al. demonstrated that the coating of nanoparticles with PVP polymer increased their half‐life and, at the same time, prevented the induction of the ABC phenomenon.…”

Tannic acid inhibits lipid metabolism and induce ROS in prostate cancer cells

“…At 70% confluence, cells were exposed to 10 and 20 µM TA for 24 h along with the untreated control. The cells (both dead and live) were pelleted, lysed, and processed for protein profiling studies [72][73][74][75][76][77] . After TA treatment, cell lysates were prepared using CelLytic M lysis buffer (sigma Aldrich, St. Louis, MO, USA).…”