Enhanced Cutaneous Delivery of Quercetin Using Poloxamer 407–Cellulose Derivative Systems: A Topical Approach Aimed at Melanoma Therapy

Abstract Skin cancer therapy still presents limitations regarding efficacy and invasiveness, which highlights the need for alternative therapeutic approaches. Quercetin has emerged as a promising natural compound because of its antioxidant, anti-inflammatory, and potential antitumor effects. However, its clinical topical application is limited by low bioavailability. The use of thermoresponsive and bioadhesive polymeric systems constitutes a promising strategy for topical administration. This study aimed to investigate formulations composed of poloxamer 407 and cellulose derivatives containing quercetin for the treatment of skin cancers. Therefore, the systems were evaluated regarding in vitro quercetin release profile, ex vivo skin permeation, micelle morphology, formulation toxicity using Artemia salina, cytotoxicity, and effects on cell proliferation using fibroblasts and melanoma cells. The formulations showed prolonged release, promoting controlled quercetin release over time, and the ability to permeate deeper skin layers. The hydrodynamic diameter was within the nanometric scale, and the systems exhibited a homogeneous micellar distribution. None of the formulations were cytotoxic or cytostatic in both fibroblasts and melanoma cell lines. The F2-Q4 altered cellular metabolic activity in melanoma cells, suggesting a modulation of cellular metabolism. Interestingly, this effect was not observed in nontumoral fibroblasts. Further studies are required to elucidate the mechanisms involved and investigate the potential of this system for topical melanoma treatment.