Silk Fibroin‐Stabilized Lapachol Microemulsion Enhances Antiglioma Activity In Vitro

ABSTRACT Gliomas are the most prevalent of the brain tumors, and are associated with high mortality and limited therapeutic options. This study introduces, for the first time, a silk fibroin (SF)‐based microemulsion as a nanocarrier for lapachol (LP). The nanocarrier demonstrated improved stability, selectivity, and antiproliferative efficacy against glioma cells, compared to conventional pharmacological approaches. The aim of this study was to evaluate the therapeutic potential of LP and two nanostructured formulations, a lapachol nanoemulsion (LPN) and an SF‐based microemulsion (LP‐SF), in human (AHOL1) and rat (C6) glioma cells. Both formulations exhibited colloidal stability, with LP‐SF showing sustained drug release and higher cytotoxicity (half‐maximal inhibitory concentration [IC 50 ] of 19.96 µg/mL for C6 and 1.7 µg/mL for AHOL1), compared to isolated LP (IC 50 of 44.7 µg/mL for C6 and 3.15 µg/mL for AHOL1) and LPN (33.9 µg/mL for C6 and 2.3 µg/mL for AHOL1). LP‐SF retained selectivity toward tumor cells, while preserving the viability of healthy cells, confirming its lack of harmful effects. These results highlight LP‐SF as a promising nanoplatform for glioma therapy, combining enhanced antitumor efficacy with safety.