Enhanced intercellular release of anticancer drug by using nano-sized catanionic vesicles of doxorubicin hydrochloride and gemini surfactants

Abstract

In this study, we provide an alternative formulation to develop gemini surfactant (GSs)–drug nano-sized catanionic vesicles with multi stimuli-responsiveness, which have great potential applications in the fields of controlled release and drug delivery in chemotherapy. The main aim of this study was to investigate how catanionic vesicles could influence the encapsulation and release of the anticancer drug Doxorubicin (DOX). The DOX was self-associated in an aqueous medium according to reported studies still controversial. We present here the simple and convenient methods, surface tension, conductance and circular dichroism (CD) studies to give direct evidence that DOX was self-associated at the critical concentration about 0.841mmolL−1. The influence of micelle based on DOX-loaded (DLs) and mixed micelle (C*(αDOX+αGSs)) catanionic vesicles (DGCs) showed the highly synergistic interaction. The physicochemical properties, molecular docking, drug uptake and release of DOX in in-vitro for DL and DGC were explored. The substantial amounts of DOX could successfully encapsulate into the catanionic vesicles. The important point of DGC vesicles was they could reduce toxicity and revealed better therapeutic effects when the DOX was in high concentration. Moreover, the cell viability of DL-12 vesicles was 44%, and DL-16 vesicles was 70% at 18μmolL−1, while at 20.0μmolL−1 it was 44% in DGC-12 as αDOX was 0.6 and 56% in DGC-16 as αDOX was 0.9. The in-vitro cytotoxicity and fluorescence microscopic images of DL and DGC vesicles on MCF-7 cell lines showed the improved nuclear localization of DOX uptakes. These findings showed the high importance of catanionic vesicles to enhance the free DOX entrance mainly via endocytosis for breast cancer cell.