Lipid-based nanocarriers coupled with CO2 laser-mediated drug delivery enhance skin penetration and hair follicle targeting.

The topical administration of hydrophilic drugs such as minoxidil and minocycline for alopecia and acne treatments remains unsatisfactory due to limited skin absorption and follicular uptake. The combination of physical and chemical enhancement methods may be beneficial in improving skin delivery. In this study, minoxidil and minocycline were topically delivered in nanoparticulate form to penetrate the skin using fractional laser microporation. Skin perforation was conducted on pig skin with a CO2 laser (2-8 mJ). The lipid-based nanocarriers increased the passive absorption of the drugs as compared to the free form, with a particularly significant increase in flux. The laser enhanced the skin deposition and flux of both free and nanoencapsulated drugs. The follicular accumulation of minoxidil in nanostructured lipid carriers (NLC) and liposomes (LP) was increased by 7- and 9-fold, respectively, with laser treatment. The laser also enhanced follicular minocycline accumulation in NLC and LP by 9- and 12-fold, respectively, compared to passive transport. Biodistribution observed through confocal microscopy illustrated that the nanoparticles were primarily transported through the laser-created microchannels, with both vertical and horizontal diffusion. After CO2 laser exposure, the nanoparticles were visualized in both epidermal and dermal layers. In an in vivo Cutibacterium acnes-infected mouse model, a 2-log reduction in bacterial colony in the skin was observed with the combined laser and NLC. Our preclinical evidence demonstrates that the combination of laser ablation with specific nanoformulations appears to be an effective and safe strategy for cutaneous and follicular delivery of hydrophilic drugs.