Biodegradable Polylactide Nanocapsules Containing Quercetin for In Vitro Suppression of Mouse B16F10 and Human Sk-Mel-28 Melanoma Cell Lines.

Quercetin is a flavonoid found in various dietary sources. It is a prodrug converted by overexpressed tyrosinase in melanoma into an active o-quinone that suppresses tumour growth. However, injected quercetin is rapidly cleared from the tumour site. Our study aimed to enhance quercetin's efficacy through nanoencapsulation using biodegradable nanocapsules, which were tested in both mouse and human melanoma cell lines in 2D and 3D models. Nanoencapsulation achieved sustained release and improved bioavailability. In mouse 2D cultures, quercetin nanocapsules (Q-nanos) reduced cell viability to 28%, compared with 46% for free quercetin (Q-only) ( < 0.05). In 3D cultures simulating in vivo conditions, Q-nanos reduced viability to 43%, showing significant anti-melanoma activity, while Q-only resulted in 72% viability ( > 0.05 vs. control). A similar trend was observed in human melanotic melanoma, where both Q-nanos and Q-only were effective compared with the controls, with Q-nanos demonstrating superior tumour inhibition ( < 0.05). These findings show the superior efficacy of nanoencapsulated quercetin over free quercetin. Nanoencapsulation prolonged quercetin's bioavailability, enhanced tumour regression, and addressed limitations associated with the rapid clearance of free quercetin.