Emulsomal nanovesicles: A Platform for boosting the oral bioavailability and selective toxicity of tamoxifen citrate towards breast cancer cells.

Abstract

The clinical applicability of Tamoxifen citrate (Tam), one of the traditional anticancer medications for breast cancer treatment, faces substantial challenges due to its poor oral bioavailability and perilous concomitant side effects emanating from its low discrimination to cancerous cells. To improve oral bioavailability and selective cytotoxicity, we developed lipid-based nanocarriers, emulsomes (EMLs), which were optimized using Box-Behnken design. The effects of three variables were surveyed: total lipid amount, phospholipid: triglyceride (PL:TG) ratio and drug concentration. The optimized formula (OF) prepared with tripalmitin scored a particle size (PS), zeta potential (ZP), and entrapment efficiency (EE%) of 177.0±2.3nm, −21.5±0.7mV, and 87.5±1.8%. The EMLs’ core was further modified using a mixture of TG (tripalmitin and glyceryl trioleate) in different ratios and the selected formula (T2) attained PS, ZP and EE% of 195.9±5.5nm, −23.0±1.3mV and 82.0±1.9%. A cytotoxicity study on MCF-7 cell lines revealed low inhibitory concentration (IC50) values of 33.4±1.2 and 32.3±1.9μg/mL for T2 and OF, respectively, compared to 58.5±2.1μg/mL for free Tam solution, with an added value of their higher selectivity against cancer cells over normal cells with excellent hemocompatibility. The in-vivo pharmacokinetic study showed substantially higher maximal blood concentration (Cmax), area under the curve (AUC0-∞), and relative bioavailability (Frelative) values for Tam-EMLs compared to Tam solution, denoting greater oral bioavailability. The achieved selective in-vitro cytotoxicity, enhanced bioavailability, extended half-life and reduced elimination, all are aspects that convey EMLs as a promising tool to address treatment-related obstacles of Tam for breast cancer for future tailoring.