Natural plant oil-based drug delivery systems influence melanoma growth in in vitro studies

This study demonstrated the design and in vitro potential of natural oil-based nanostructured lipid carriers (NLCs) loaded with quercetin (QR), using olive oil (OO) and rosemary oil (RO), evaluated for their effects on melanoma progression using a melanoma skin model (MSm). QR was encapsulated in NLCs with only OO (QR-OO-NLC), RO (QR-RO-NLC) and a mixture of both oils (QR-30RO30OO-NLC) in their composition. The particle size ranged from 177 ± 7 nm for QR-30RO30OO-NLC to 199 ± 10 nm for QR-RO-NLC. The zeta potential remained above |30| mV for all systems. QR-loaded NLCs exhibited strong antioxidant activity, with values ranging between 81% (QR-RO-NLC) and 87% (QR-OO-NLC). In addition, quercetin-loaded systems demonstrated no irritation effect in 3D cytotoxicity assays. The intracellular accumulation of QR in the perinuclear space and within the nucleus revealed that QR-loaded NLCs could penetrate human dermal fibroblasts, keratinocytes, and melanoma cells, delivering quercetin to the nucleus. Permeation studies in 3D skin models showed a biphasic release pattern: a rapid initial burst followed by sustained release. After 24 hours, the cumulative permeation of quercetin ranged from 83.1 μg/cm 2 for QR-OO-NLC to 101.7 μg/cm 2 for QR-30RO30OO-NLC in full-thickness skin, and from 20.5 μg/cm 2 for QR-RO-NLC to 48.3 μg/cm 2 for QR-OO-NLC in melanoma skin. Histological analysis of melanoma skin models treated with the QR-loaded carriers indicated an absence of superficial melanoma and reduced dermal tumour clusters, while preserving epidermal cohesion. Fluorescence microscopy further demonstrated significant particle accumulation in the epidermis, with limited diffusion into the dermis. This research advances the use of natural plant oils with antitumour potential, combined with antimelanoma bioactive compounds, to develop natural oil-based lipid nanocarriers for topical therapy. • Natural oils yield nanocarriers suitable for the topical treatment of melanoma. • Quercetin-loaded nanocarriers exhibit biphasic quercetin diffusion. • Intranuclear uptake of quercetin from loaded nanocarriers in melanoma cells. • Quercetin-loaded nanocarriers may inhibit melanoma growth on a melanoma skin model.