Nanostructured lipid carriers loaded with an association of minoxidil and latanoprost for targeted topical therapy of alopecia.

Alopecia is a condition associated with different etiologies, ranging from hormonal changes to chemotherapy, that affects over 80 million people in the USA. Nevertheless, there are currently few FDA-approved drugs for topical treatment, and existing formulations still present skin irritation issues, compromising treatment adherence. This work aimed to develop a safe formulation based on nanostructured lipid carriers (NLC) that entrap an association of minoxidil and latanoprost and target drug delivery to the hair follicles. To do so, thermal techniques combined with FTIR were used to assess the chemical compatibility of the proposed drug association. Then, NLC with 393.5 ± 36.0 nm (PdI < 0.4) and +22.5 ± 0.2 mV zeta potential were produced and shown to entrap 86.9% of minoxidil and 99.9% of latanoprost efficiently. In vitro, the free drug combination was indicated to exert positive effects over human primary epidermal keratinocytes, supporting cell proliferation, migration and inducing the mRNA expression of MKI67 proliferation marker and VEGF - a possible effector for minoxidil-mediated hair growth. Interestingly, such a favorable drug combination profile was optimized when delivered using our NLC. Furthermore, according to the HET-CAM and reconstructed human epidermis assays, the nanoformulation was well tolerated. Finally, drug penetration was evaluated in vitro using porcine skin. Such experiments indicated that the NLC could be deposited preferentially into the hair follicles, causing a considerable increase in the penetration of the two drugs in such structures, compared to the control (composed of the free compounds) and generating a target-effect of approximately 50% for both drugs. In summary, present results suggest that hair follicle-targeted delivery of the minoxidil and latanoprost combination is a promising alternative to treat alopecia.