A Smart Paclitaxel-Disulfiram Nanococrystals for Efficient MDR Reversal and Enhanced Apoptosis

Pharmaceutical Research
Imran Shair MohammadLifang Yin

Abstract

A multidrug resistance (MDR) modulator, disulfiram (DSF), was incorporated into pure paclitaxel (PTX) nanoparticles to construct a smart paclitaxel-disulfiram nanococrystals (PTX-DSF Ns) stabilized by β-lactoglobulin (β-LG), with the aim to reverse MDR and therefore enhnce cytotoxicity towards Taxol-resistant A549 cells (A549/TAX). PTX-DSF Ns was prepared by antisolvent precipitation method. Flow cytometry was used to determine the cell uptake, drug efflux inhibition, cell cycle phase arrest and apoptosis. MDR-1 gene expression level was detected by real time quantitative PCR and gel electrophoresis. PTX-DSF Ns prepared from the optimized formulation had an optimum diameter of 160 nm, was stable and had a high drug-loading capacity. Importantly, the uptake of PTX-DSF Ns in A549/TAX cells was 14-fold greater than the uptake of PTX Ns. Furthermore, PTX-DSF Ns promoted 5-folds increase in apoptosis, enabled 7-folds reduction in the IC50, and rendered 8.9-fold decrease in the dose compared with free PTX. PTX-DSF Ns with a precise mass ratio offer efficient cytotoxicity against Taxol-resistant cells and a novel approach for codelivery and sensitizing MDR cancer to chemotherapy. In addition, the use of nanosuspensions as a combined t...Continue Reading

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Citations

May 16, 2019·Recent Patents on Anti-cancer Drug Discovery·Elmira EkinciQingping P Dou
Nov 24, 2019·Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences·Muhammad Asim FarooqBo Wang
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Aug 25, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Imran Shair MohammadHaji Muhammad Shoaib Khan

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Methods Mentioned

BETA
PCR
dynamic light scattering
X-Ray
Circular Dichroism
fluorescence spectroscopy
flow cytometry
electrophoresis

Software Mentioned

CompuSyn
GraphPad
Quant Studio 3
GraphPad Prism

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

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Antimicrobial Resistance (ASM)

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