Back to Search Start Over

Drug-delivering-drug approach-based codelivery of paclitaxel and disulfiram for treating multidrug-resistant cancer

Authors :
Imran Shair Mohammad
Birendra Chaurasiya
Lifang Yin
Chunyong Wu
Chao Teng
Wei He
Source :
International Journal of Pharmaceutics. 557:304-313
Publication Year :
2019
Publisher :
Elsevier BV, 2019.

Abstract

Multidrug resistance (MDR) is a common intractable barrier in success of clinical cancer chemotherapy. Codelivery of two drugs using nanocarriers is a commonly used approach to treat the MDR cancer. However, the drug payload in the conventional nanocarriers is low and thus compromises the treatment outcomes. Disulfiram (DSF) is promising to reverse MDR and increases the sensitivity of cancer cells to chemotherapy. While, paclitaxel (PTX) is one of the frequently used anticancer drug. Here, by using a drug-delivering-drug (DDD) strategy based on nanocrystals, hybrid PTX-DSF nanocrystals (PTX-DSF Ns) were developed for codelivery of PTX and DSF to reverse MDR in cancer. The 160-nm PTX-DSF Ns with rod-like morphology had drug-loading up to 43% at mass ratio of 5:1. Interestingly, the nanoparticles entered cells via caveolar endocytosis. By reducing intracellular ATP level and GST activity, PTX-DSF Ns killed the Taxol resistant A549 cells with higher efficiency than PTX alone, exhibiting as 6-fold increase of apoptosis in MDR tumor. The nanoparticles circulated in blood over time, accumulated in tumor efficiently and reduced the tumor volume by 12-fold in MDR tumor-bearing BALB/c nude mice and allowed 12-fold apoptosis in tumor. Additionally, the immunohistochemical examination demonstrated the safety of the nanoparticles. Overall, the DDD strategy-based PTX-DSF Ns have promising potential for the treatment of MDR cancer.

Details

ISSN :
03785173
Volume :
557
Database :
OpenAIRE
Journal :
International Journal of Pharmaceutics
Accession number :
edsair.doi.dedup.....73cad8e2697e419b9d605dee54184199
Full Text :
https://doi.org/10.1016/j.ijpharm.2018.12.067