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

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 mu M for curcumin-loaded MSNs and 163.313 +/- 12.880 mu M 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.