Lipid-based nanocarriers as versatile platforms for curcumin delivery in photodynamic therapy of skin cancer

Non-melanoma skin cancer is one of the most frequent tumors, ranking as the fifth most common cancer. Photodynamic therapy is a noninvasive therapeutic option that involves the topical application of photosensitizers. In this context, curcumin, a polyphenolic compound extracted from Curcuma longa L., emerges as a safe alternative because of its potential phototoxic activity; however, it presents limitations such as poor skin penetration upon topical application and photodegradation. Among the promising strategies, the development of lipid nanoparticles, which are biocompatible and versatile systems, is noteworthy. In the present study, three curcumin lipid nanoparticles (LNPs) were developed and characterized, containing oleic acid, super refined castor oil, Phosal 50SA®, and Phosal 50PG® in PBS buffer, with 1.5% Poloxamer 407. The formation of these liquid crystalline phases was investigated. The LNPs exhibited mean particle sizes of 176 ± 6 nm(A1Cur), 169 ± 9 nm(C2Cur), 189 ± 19 nm(H3Cur), with corresponding PDIs of 0.133 ± 0.034; 0.226 ± 0.022 and 0.196 ± 0.009, and zeta potentials of -33 ± 1 mV; -26 ± 2 mV; -24 ± 2 mV for A1Cur, C2Cur and H3Cur, respectively. The encapsulation efficiency (EE%) was 89 ± 5% for A1Cur, 84 ± 6% for C2Cur, and 69 ± 6% for H3Cur, respectively. Small angle X-ray scattering (SAXS) revealed that only A1Cur exhibited a hexagonal liquid-crystalline phase morphology. In terms of in vitro skin penetration, A1Cur, C2Cur, and free curcumin exhibited transdermal effects, while H3Cur demonstrated greater topical potential. In ROS photogeneration assays, photoproduction was detected, particularly for LNP H3Cur. In vitro 24-hour cytotoxicity and phototoxicity against the A431 tumor cell line demonstrated that the cytotoxic and phototoxic effects were enhanced by the LNPs compared to free curcumin, especially for A1Cur. The liquid crystalline nanodispersions A1 and A1Cur were selected for incorporation into the dissolving microneedle systems, exhibiting good insertion capability and mechanical resistance to pressure. The LNPs demonstrated skin penetration potential and enhanced phototoxic and cytotoxic effects on a non-melanoma skin carcinoma cell line compared to free curcumin, highlighting the potential of these nanosystems as drug delivery vehicles for the treatment of non-melanoma cancer.