Simultaneous encapsulation of dasatinib and celecoxib into caseinate micelles towards improved in vivo anti-breast cancer efficacy with reduced drug toxicity

Breast cancer is the most global dominant cancer among females. Although there are continuously growing strategies to develop new therapies, the outcomes are usually insufficient. Simultaneous combinational therapy using more than one drug is a promising strategy to treat breast cancer. Yet, administration of these drugs in their free form is usually associated with diverse side effects. Nanoencapsulation can afford entrapping drugs within the same nanocarrier for enhanced effect. Protein micelles have been widely utilized in nanoencapsulation owing to their biocompatibility and stability. In this study, dasatinib (DAS) and celecoxib (CXB) were co-encapsulated in the hydrophobic inner core of sodium caseinate micelles via a facile encapsulation method. In vitro cytotoxicity study for the prepared micelles was conducted on MCF-7 (hormone sensitive) and MDA-MB-231 (Triple negative) human breast cancer cell lines to evaluate their anti-cancer effect. Furthermore, the antitumor efficacy and the toxicity of the prepared micelles were examined in breast cancer animal model. Dual drug-loaded micelles revealed improved cytotoxic and synergistic effect against the examined cancer cell lines when compared to free drugs combination. More importantly, in vivo studies demonstrated enhanced antitumor effect with increased apoptosis, reduced angiogenesis, proliferation and migration. In addition, this nanoplatform was found to minimize the cytotoxic effects of both DAS and CXB. In conclusion, utilization of DAS/CXB-loaded sodium caseinate micelles can act as a promising drug delivery platform with increased drugs sensitization and minimized toxicity.