Optimized Mesoporous Silica Nanoparticles for Delivery of Curcumin and Quercetin: Enhanced Skin Permeation and Cytotoxicity Against A375 Melanoma Cells

Abstract

Melanoma, the most aggressive skin cancer, requires novel and effective treatment strategies. This study developed an optimized mesoporous silica nanoparticle (MSN)-based system for the delivery of curcumin and quercetin, two polyphenolic compounds with anticancer properties, to enhance their transdermal delivery. MSNs were synthesized using the sol-gel method and optimized via a Box-Behnken design, resulting in nanoparticles with an average size of 172.92 ± 23.74 nm and a polydispersity index (PDI) of 0.291 ± 0.026. Drug entrapment efficiencies were 46.25 ± 3.55% for curcumin and 50.35 ± 4.65% for quercetin. In vitro drug release showed sustained profiles, with 8.49 ± 0.80% of curcumin and 12.87 ± 1.27% of quercetin released over 24 h. Ex vivo skin permeation studies revealed a 2.6-fold and 2.25-fold increase in permeation for curcumin and quercetin, respectively, compared to free drugs. Cytotoxicity studies demonstrated enhanced efficacy of the co-delivered MSNs formulations, with IC₅₀ values of 91.351 ± 6.114 µM for curcumin-loaded MSNs and 163.313 ± 12.880 µM for quercetin-loaded MSNs against A375 melanoma cells, significantly lower than those of their free drug counterparts. These findings suggest that MSN-based delivery systems offer a promising strategy for the topical treatment of melanoma by improving drug permeation and therapeutic efficacy.