Dihydroartemisinin and doxorubicin co-loaded Soluplus®-TPGS mixed micelles: formulation characterization, cellular uptake, and pharmacodynamic studies

Clinically, co-delivery of chemotherapeutics has been limited by poor water-solubility and severe systemic toxicity. This study was aimed at integrating the merits of combination chemotherapy and mixed micellar technology and demonstrating the anticancer potential of doxorubicin (DOX) and dihydroart...

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Bibliographic Details
Published in:Pharmaceutical development and technology 2019-10, Vol.24 (9), p.1125-1132
Main Authors: Wang, Yutong, Ding, Yanfang, Zhao, Jing, Wang, Changyuan, Gao, Meng, Chi, Xinming, Zhang, Baojing, Ma, Xiaodong, Li, Lei
Format: Article
Language:English
Subjects:
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - pharmacology
Antimalarials - administration & dosage
Antimalarials - pharmacology
Artemisinins - administration & dosage
Artemisinins - pharmacology
Breast Neoplasms - drug therapy
cancer therapy
co-delivery
dihydroartemisinin
Doxorubicin
Doxorubicin - administration & dosage
Doxorubicin - pharmacology
Drug Carriers - chemistry
Drug Combinations
Female
Humans
MCF-7 Cells
Micelles
mixed micelles
Polyethylene Glycols - chemistry
Polyvinyls - chemistry
Vitamin E - chemistry
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Summary:Clinically, co-delivery of chemotherapeutics has been limited by poor water-solubility and severe systemic toxicity. This study was aimed at integrating the merits of combination chemotherapy and mixed micellar technology and demonstrating the anticancer potential of doxorubicin (DOX) and dihydroartemisinin (DHA) co-loaded Soluplus ® -TPGS mixed micellar system. In this study, physiochemically stable multidrug loaded mixed micelles were successfully prepared, encapsulation efficiencies of DOX and DHA were as high as 90%, and the average diameter of the micelles was 64.27 nm. The cellular uptake of DOX from the mixed micelles increased by 1.3 and 1.2 times for MCF-7 and MCF-7/ADR cell lines, respectively. The micelles were more cytotoxic than free DHA-DOX. Surprisingly, the co-loaded mixed micelles exhibited higher antitumor activity, while the systemic toxicity was reduced during the treatment. Therefore, the DOX and DHA mixed micelle might be a potential, effective, and less toxic drug-delivery system for cancer therapy.
ISSN:1083-7450
1097-9867
DOI:10.1080/10837450.2019.1641726