Squalene-containing nanostructured lipid carriers promote percutaneous absorption and hair follicle targeting of diphencyprone for treating alopecia areata.

PURPOSE: Diphencyprone (DPCP) is a therapeutic agent for treating alopecia areata. To improve skin absorption and follicular targeting nanostructured lipid carriers (NLCs) were developed.

METHODS

Nanoparticles were characterized by size, zeta potential, molecular environment, differential scanning calorimetry (DSC), and nuclear magnetic resonance (NMR). In vitro and in vivo skin absorption experiments were performed. Fluorescence and confocal microscopes for imaging skin distribution were used.

RESULTS

NLCs with different designs were 208 ~ 265 nm with  > 77% DPCP encapsulation. NLCs incorporating a cationic surfactant or more soybean phosphatidylcholine (SPC) showed higher lipophilicity compared to typical NLCs by Nile red emission. All NLCs tested revealed controlled DPCP release; burst release was observed for control. The formulation with more SPC provided 275 μg/g DPCP skin retention, which was greater than control and other NLCs. Intersubject deviation was reduced after DPCP loading into NLCs. Cyanoacrylate skin biopsy demonstrated greater follicular deposition for NLCs with more SPC compared to control. Cationic NLCs but not typical or SPC-containing carriers were largely internalized into keratinocytes. In vivo skin retention of NLCs with more SPC was higher than free control. Confocal imaging confirmed localization of NLCs in follicles and intercellular lipids of stratum corneum.

CONCLUSIONS

This work encourages further investigation of DPCP absorption using NLCs with a specific formulation design.