Development and evaluation of sorafenib and curcumin co-loaded microemulsion gel for the management of breast cancer.

In this study, sorafenib (an established anticancer drug) and curcumin (a polyphenolic compound), both with numerous challenges like solubility, permeation, bioavailability, and dose-dependent toxicity, were co‑loaded in a microemulsion-based hydrogel for breast cancer management by the topical route. Based on the solubility studies, Capmul MCM was selected as the oil, and the surfactant mixture was selected as Labrasol and Tween‑80. A total of three pseudoternary phase diagrams were explored to select the optimum composition. Out of three studied compositions, the selected one exhibited a globule size of 100.7 ± 6.83 nm with a polydispersity index value of 0.239, zeta potential of -8.14 ± 1.61 mV, and pH of 5.7 ± 0.2. The developed Carbopol-based hydrogel offered shear‑thinning rheology with appreciable spreadability, higher drug content, and skin-compatible pH. MCF‑7 cell-based cytotoxicity studies not only established the substantial decrease in the IC₅₀ values for both sorafenib and curcumin when co‑delivered but also offered a combination index < 1, indicating synergism. Rodent skin permeation studies offered a higher release flux and drug retention for both the drugs vis-à-vis the conventional gel, and the dermatokinetics proved the skin delivery potential of the developed system with elevated Cmax, permeation rates, and AUC, and also slower elimination for sorafenib. The studies established the synergism of both drugs and provided a proof of concept for enhanced topical delivery with substantial in vitro anticancer effect that can be further explored in the in vivo models.