ABSTRACT
The use of lipid nanocarriers for drug delivery applications is an active research area, and a great interest has particularly been shown in the past two decades. Among different lipid nanocarriers,
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 -tubulin stabilization. These results support the hypothesis that PVP/PTX-SAs improved paclitaxel delivery to cancer cells.
ABSTRACT
Objective: To prepare the self-assemblies of a phosphoryl N-tetradecanoyl gemcitabine (CPTG) derivative and evaluate the properties and anti-tumor effect. Methods: CPTG derivative was synthesized. The prodrug membrane was investigated using a Langmuir trough. The self-assembly was prepared using the injection method. The morphology of self-assemblies was observed by a transmission electron microscope. The particle distribution was measured by a dynamic light scattering instrument. The pharmacodynamic effect was evaluated on HepG2 cells and tumor-bearing mice. Results: The prodrug was synthesized with gemcitabine as the raw material. The surface pressure-molecular area (π-a) curves at the air/water interface indicated that the prodrug was amphiphilic and formed the stable monolayer. The self-assemblies formed the vesicles with the mean size of 93.52 nm and the Zeta potential of -31 mV. The inhibitory effects of self-assemblies were significantly higher than those of gemcitabine on the models of HepG2 cells and the tumor-bearing mice. Conclusion: The self-assemblies of the amphiphilic prodrug of gemcitabine might be a promising novel nanomedicine for targeted therapy of liver cancer.