Oral Nanomedicine Based on Multicomponent Microemulsions for Drug-Resistant Breast Cancer Treatment

• Published in: Biomacromolecules Vol. 18; no. 4; pp. 1268 - 1280
• Main Authors: Qu, Ding, Wang, Lixiang, Liu, Meng, Shen, Shiyang, Li, Teng, Liu, Yuping, Huang, Mengmeng, Liu, Congyan, Chen, Yan, Mo, Ran
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 10.04.2017
• Subjects: Administration, Oral; Animals; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - chemistry; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis - drug effects; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Caco-2 Cells; Coix - chemistry; Drug Liberation; Drug Resistance, Neoplasm - drug effects; Drug Synergism; Emulsions; Etoposide - administration & dosage; Etoposide - chemistry; Etoposide - pharmacokinetics; Etoposide - therapeutic use; Excipients; Female; Ginsenosides - administration & dosage; Ginsenosides - chemistry; Ginsenosides - pharmacokinetics; Ginsenosides - therapeutic use; Humans; Mammary Neoplasms, Experimental - drug therapy; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - pathology; MCF-7 Cells; Mice, Inbred ICR; Mice, Nude; Nanostructures - chemistry; Plant Oils - administration & dosage; Plant Oils - chemistry; Plant Oils - pharmacokinetics; Plant Oils - therapeutic use; Rats, Sprague-Dawley; Seeds - chemistry; Xenograft Model Antitumor Assays
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/acs.biomac.7b00011

The aim of this study is to demonstrate the enhanced therapeutic efficacy of anticancer drugs on drug-resistant breast cancer using multicomponent microemulsions (ECG-MEs) as an oral delivery system. The etoposide-loaded ECG-MEs were composed of coix seed oil and ginsenoside Rh2 (G-Rh2), both of which possess not only the synergistic antitumor effect with etoposide, but also have excipient-like properties. Orally administrated ECG-MEs were demonstrated to be able to accumulate at the tumor site following crossing the intestines as intact vehicles into the blood circulation. The spatiotemporal controlled release characteristics of ECG-MEs brought about the efficient P-gp inhibition by the initially released G-Rh2 and the increased intracellular accumulation of the sequentially released etoposide. The combination antitumor activity of etoposide, G-Rh2 and coix seed oil using ECG-MEs was verified on the xenograft drug-resistant breast tumor mouse models. In addition, the safety evaluation studies indicated that treatment with ECG-MEs did not cause any significant toxicity in vivo. These findings suggest that ECG-MEs as an oral formulation may offer a promising strategy to treat the drug-resistant breast cancer.