Saman Sargazi - Cellular and Molecular Research Center, Research Institute of Cellular and Molecular Sciences in Infectious Diseases, Zahedan University of Medical Sciences, Zahedan ۹۸۱۶۷۴۳۴۶۳, Iran
Mahmood Barani - Medical Mycology and Bacteriology Research Center, Kerman University of Medical Sciences ۷۶۱۶۹-۱۳۵۵۵, Kerman, Iran
Farshid Zargari - Department of Chemistry, Faculty of Science, University of Sistan and Balouchestan, Zahedan, Iran
Rabia Arshad - Department of Pharmacy, Quaid-i-Azam University, Islamabad ۴۵۳۲۰, Pakistan
Rakesh K. Sharma - Applied Chemistry Department, Faculty of Technology and Engineering, The M. S. University of Baroda, Vadodara, Gujarat, India

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 ۱۲۵ nm, a surface charge of -۲۲.۷ mV, a DOX encapsulation efficiency (EE) of ۷۰.۸%, 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 ۶۰, Span ۶۰, 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 MCF۷ breast cancer cell line was evaluated. Compared with free administered DOX, we found lower IC۵۰ values for the MCF۷ cells exposed to niosomal DOX (۱.۱۵۳ vs. ۰.۲۲۹ after ۲۴ h, ۰.۷۹۶ vs. ۰.۱۴۸ µg/mL after ۴۸ h, and ۰.۴۶۱ vs. ۰.۰۸۱ µg/mL after ۷۲ h of incubation, respectively). Additionally, niosomal DOX-induced apparent morphological alterations in MCF۷ 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.

doxorubicin, Niosomes, In-silico analysis, Nanocarrier, pH-Responsiveness, Vesicle