Preparation of pH-Responsive Vesicular Doxorubicin: Evidence from In-Vitro and In-Silico Evaluations

Colloidal nanocarriers have provided great opportunities in the field of drug delivery. In this study, to achieve the efficient delivery of anti-cancer agents at the site of action, doxorubicin (DOX) was encapsulated within pH-responsive ergosterol-modified niosomes. The niosome-based formulation displayed size of 125 nm, a surface charge of -22.7 mV, a DOX encapsulation efficiency (EE) of 70.8%, and pH-responsive release behavior. An in-silico approach was conducted to analyze the interactions of the loaded drug with the niosome bilayer and to evaluate the structural and dynamical properties of the loaded nanovehicle by constructing a niosome bilayer model containing Tween 60, Span 60, and ergosterol molecules. Computational analyses revealed that the  a-hydroxy ketone and daunosamine moieties of DOX are responsible for its arrangement towards the niosome bilayer. On the other hand, the cytotoxic activity of encapsulated DOX compared with its free form in an MCF7 breast cancer cell line was evaluated. Compared with free administered DOX, we found lower IC50 values for the MCF7 cells exposed to niosomal DOX (1.153 vs. 0.229 after 24 h, 0.796 vs. 0.148 µg/mL after 48 h, and 0.461 vs. 0.081 µg/mL after 72 h of incubation, respectively). Additionally, niosomal DOX-induced apparent morphological alterations in MCF7 cells. Hence, we showed that niosomes are promising nanocarriers that can be used to encapsulate and release well-established anti-cancer drugs in order to improve their release and, thus biological activity and therapeutic efficacy.