Fractional microporation-guided delivery of nanoencapsulated drugs for enhanced cutaneous and follicular absorption: a comparison of ablative laser and radiofrequency microneedling

The use of fractional microporation to disrupt superficial skin is an effective approach to enhance drug absorption. This study analyzed and compared the effectiveness of fractional Er:YAG laser and radiofrequency microneedling (RM) in promoting skin penetration and hair follicle (HF) targeting of free or nanoencapsulated minoxidil and minocycline. Porcine skin delivery, with or without laser (3, 6, and 7 mJ) and RM (6.1, 10.2, and 20.4 mJ with a penetration depth of 0.5 or 1.0 mm), was investigated using in vitro permeation test (IVPT). The in vitro and in vivo antibacterial activity of the microporation-assisted minocycline-loaded nanocarriers was also conducted. The skin deposition and flux of free minoxidil were increased by 3- and 56-fold, respectively, with laser treatment at 7 mJ. The laser enhanced the deposition and flux of free minocycline by 25- and 40-fold compared to the untreated control, respectively. RM elevated the drug flux by 5‒18-fold compared to passive absorption. However, this enhancement effect was not observed in skin deposition. Nanostructured lipid carriers (NLC) and liposomes, with sizes of 81 and 76 nm, were produced and entrapped approximately 80% of the drugs, respectively. Microporation increased skin delivery of nanoencapsulated drugs, though this enhancement was less pronounced than that of the free drugs. Biodistribution observed through confocal microscopy showed that microporation increased the penetration depth of lipid-based nanocarriers into the dermis compared to passive diffusion. The nanocarriers were primarily distributed into the microchannels and transported into the surrounding dermal tissue. Minocycline uptake in HF increased from 0.03 to 0.16 and 0.20 nmol/cm² after the nanoencapsulation with NLC and liposomes, respectively. This uptake of NLC was further increased to 1.24 and 1.51 nmol/cm² by laser and RM treatment. The minocycline-loaded nanocarriers inhibited Cutibacterium acnes viability in both planktonic and biofilm forms more effectively than the free drug. The in vivo C. acnes infection model in mice exhibited an efficient bacterial eradication through microporation-mediated nanocarrier delivery. The microchannel closure in laser- and RM-treated skin occurred within 36 and 12 h, respectively, as indicated by transepidermal water loss (TEWL). These findings demonstrate that fractional laser and RM are promising strategies for improving skin- and HF-targeted absorption of nanoencapsulated drugs.