Self-assembled and pH-sensitive mixed micelles as an intracellular doxorubicin delivery system

Abstract

Nanocarrier-based drug delivery systems have been explored extensively in cancer therapy. Among the vast number of different nanocarrier systems applied to deliver chemotherapeutics to cancer tumor, intelligent systems which deliver drug to various sites in the body have attracted considerable attentions. Finding a specific stimulant that triggers the carrier to release its payload in the target tissue is a key parameter for efficacy of delivery systems. Acidic pH of cancer tumor helps a pH-sensitive carrier to release drug at the tumor site. In this study, a pH-sensitive mixed micellar system was developed using Dextran-Stearic Acid (Dex-SA) and Dextran-Histidine (Dex-His) conjugated polymers to deliver doxorubicin (DOX) to cancer cells. Drug release from this micellar system showed higher release rate at acidic pH than that of in neutral environment, where the release was 56 and 76% at pH 7.4 and acidic pH, respectively. Finally, the in vitro cytotoxicity and cell uptake of DOX-loaded micelles and free DOX on U87 MG cell line showed that micellar systems had more anti-proliferation effect and uptake compared to free drug.