Curcumin-loaded lipid nanoparticles for photodynamic therapy in the topical treatment of melanoma.

Abstract

Melanoma remains one of the deadliest skin cancers, and current therapies still struggle to combine efficacy with minimal invasiveness. Photodynamic therapy (PDT) is a promising alternative, yet its translation is hindered by poor photosensitizer (PS) solubility and difficulty achieving effective localized skin delivery. This study developed multifunctional curcumin (Cur)-loaded solid lipid nanoparticles (Cur-SLN) and nanostructured lipid carriers (Cur-NLC) for topical PDT, incorporating lauric acid in both formulations and,in Cur-NLC, menthol to provide complementary functional properties to the lipid-based delivery system. Physicochemical characterization revealed mean particle sizes of 209 ± 4 nm (Cur-SLN) and 226 ± 9 nm (Cur-NLC), polydispersity indices below 0.3, negative surface charges of approximately - 20 mV, and high encapsulation efficiencies (76-78%). Both formulations demonstrated good stability and sustained Cur release. Franz diffusion studies using porcine skin showed no detectable Cur in the receptor compartment after 24 h, indicating negligible transdermal permeation. In vitro studies in L929 fibroblasts, HaCaT keratinocytes, and A375 melanoma cells showed a cytocompatible profile (≥70% viability) under non-irradiated conditions, while Cur-SLN and Cur-NLC reduced melanoma cell viability to < 15% upon blue light irradiation (420 nm), with PDT-mediated melanoma cell killing comparable to free Cur. Confocal microscopy showed a higher intracellular Cur-associated fluorescence signal in cells treated with Cur-NLC than in cells treated with Cur-SLN. Overall, Cur-loaded lipid nanoparticles demonstrated favourable physicochemical properties, sustained Cur release, good cytocompatibility, and strong PDT activity against melanoma cells, supporting their potential as topical PDT formulations with negligible transdermal permeation.