Fractional ablative laser-enhanced transdermal delivery of vismodegib: systematic evaluation of microporation parameters and permeation kinetics

This research investigates the in vitro transdermal permeation of vismodegib through dermatomed human skin following fractional laser ablation. Skin samples were exposed to varying laser fluence, pore density, and drug concentration (The Precise Laser Epidermal System platform, P.L.E.A.S.E® system). Successful dermal microporation was verified through dye binding analysis, histological examination, microchannel uniformity assessment, confocal microscopy, and scanning electron microscopy evaluation. Skin barrier integrity was characterized via transepidermal water loss and electrical resistance measurements. Permeation experiments utilized Franz cells to quantify drug penetration into and through dermal tissues. Laser ablation generated uniform microchannels within the skin tissue. Confocal microscopic analysis demonstrated that enhanced laser fluence led to the development of deeper microchannels. Substantial increase in transepidermal water loss coupled with reduced electrical resistance confirmed disruption of barrier function. During permeation experiments, all laser-processed groups exhibited significantly greater drug accumulation within receptor compartments and skin layers compared to the control (p < 0.05). An increase in laser energy, pore density, and drug concentration yielded statistically significant enhancement in drug permeation, flux, diffusion coefficient, permeability coefficient, and predicted steady-state plasma concentration, while simultaneously producing a marked reduction in lag time (n = 4, p < 0.05). Drug quantities within skin layers, cumulative delivery, delivery efficiency, and topical selectivity were additionally studied and reported. Fractional ablative laser treatment substantially enhanced transdermal permeation of vismodegib into and through dermal tissues.

Characterization; Fractional ablative laser; Permeation; Skin delivery; Vismodegib.