Imran Shair Mohammad1, Wei He2, Lifang Yin3,4. 1. Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. 2. Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. weihe@cpu.edu.cn. 3. Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. lifangyin_@163.com. 4. Key Laboratory of Druggability of Biopharmaceutics, China Pharmaceutical University, Nanjing, 210009, People's Republic of China. lifangyin_@163.com.
Abstract
PURPOSE: 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). METHOD: 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. RESULTS: 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. CONCLUSION: 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 treatment provides a new research avenue for nanosuspensions.
PURPOSE: 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). METHOD: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. RESULTS: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. CONCLUSION: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 treatment provides a new research avenue for nanosuspensions.
Authors: S Gorinstein; I Goshev; S Moncheva; M Zemser; M Weisz; A Caspi; I Libman; H T Lerner; S Trakhtenberg; O Martín-Belloso Journal: J Protein Chem Date: 2000-11
Authors: Muhammad Asim Farooq; Md Aquib; Daulat Haleem Khan; Zahid Hussain; Anam Ahsan; Mirza Muhammad Faran Ashraf Baig; Dickson Pius Wande; Muhammad Masood Ahmad; Hafiz Muhammad Ahsan; Jiang Jiajie; Bo Wang Journal: Daru Date: 2019-11-22 Impact factor: 3.117