Modular self-emulsifying drug delivery platform to enhance cellular uptake activity in triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) presents with resistance phenotypes to certain therapies, such as cisplatin, often requiring higher dosing, with associated acquired tumor resistance, renal toxicity, and variable patient responses. A self-emulsifying drug delivery (SEDD) formulation approach was proposed to overcome the limitations of cisplatin in TNBC, focusing on improving intracellular cisplatin and control siRNA uptake as a proof-of-principle of dual drug delivery. Four SEDD formulations were prepared and optimized for cisplatin (o/w) emulsion and FITC-siRNA (w/o) emulsion using pseudo-ternary phase diagrams to facilitate the formation of water-in-oil-water (w/o/w) emulsions. Formulations were characterized by size, polydispersity (PDI), and surface charge and tested in vitro. Cellular uptake via triplex staining of drug-loaded SEDDs was investigated. SEDDs showed enhanced internalization and promoted selective TNBC cellular uptake. The current study is a proof-of-principle for the successful co-delivery of cisplatin (small molecule) and siRNA (large molecule) via the SEDDs platform.