Pharmaceutical Research

, 35:77 | Cite as

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

  • Imran Shair Mohammad
  • Wei He
  • Lifang Yin
Research Paper



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 treatment provides a new research avenue for nanosuspensions.


apoptosis combined therapy multidrug resistance nanosuspensions p-glycoprotein 



Sensitive human lung adenocarcinoma cell line


Taxol resistant human lung adenocarcinoma cell line


ATP-Binding Cassette


Bicinchoninic acid




Circular Dichroism


Complementary DNA


Combination index


Confocal laser scanning microscope


4, 6-diamidino-2-phenylindole


Drug loading


Dynamic light scattering


Dimethyl sulfoxide


Dose reduction index




Encapsulation efficiency


Fetal bovine serum


Food and Drug administration


Fluorescein 5(6)-isothiocyanate


High-performance liquid chromatography


Half maximal inhibitory concentration


Multidrug resistance


Multidrug resistance gene-1


3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide


Phosphate buffer saline


Polydispersity index




Propidium iodide




Free Paclitaxel-Disulfiram formulation


Paclitaxel-Disulfiram nanococrystals


Powder X-ray Diffraction


Ribonucleic acid


Real time quantitative PCR


Scanning electron microscopy


Transmission electron microscopy




Acknowledgments and Disclosures

This study was supported by grants from the National Natural Science Foundation of China (Nos. 81673377, 81473152, and 81402869), the Natural Science Foundation of Jiangsu Province (No. BK20140671), and the Fostering Plan of University Scientific and Technological Innovation Team and Key Members of the Outstanding Young Teacher of Jiangsu Qing Lan Project (2014 and 2016). We also thank Xiaonan Ma, Minhui Sun and Yingjian Hou from the Cellular and Molecular Biology Center of China Pharmaceutical University for providing technical assistance. The authors report no conflicts of interest with this work.

Supplementary material

11095_2018_2370_MOESM1_ESM.docx (1.3 mb)
ESM 1 (DOCX 1281 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pharmaceutics, School of PharmacyChina Pharmaceutical UniversityNanjingPeople’s Republic of China
  2. 2.Key Laboratory of Druggability of BiopharmaceuticsChina Pharmaceutical UniversityNanjingPeople’s Republic of China

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