Enhanced uptake and photoactivation of topical methyl aminolevulinate after fractional CO₂ laser pretreatment

Abstract

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) of thick skin lesions is limited by topical drug uptake. Ablative fractional resurfacing (AFR) creates vertical channels that may facilitate topical PDT drug penetration and improve PDT-response in deep skin layers. The purpose of this study was to evaluate whether pre-treating the skin with AFR before topically applied methyl aminolevulinate (MAL) could enable a deep PDT-response. MATERIALS AND METHODS: Yorkshire swine were treated under general anesthesia with a fractional CO(2) laser using stacked single pulses of 3 milliseconds, 91.6 mJ per pulse and subsequent topical MAL application for 3 hours (Metvix®). Red light (LED arrays) was then delivered at fluences of 37 and 200 J/cm(2). Fluorescent photography and microscopy was used to quantify MAL-induced porphyrin distribution and PDT-induced photobleaching at the skin surface and five specific depths down to 1,800 µm. RESULTS: Laser-ablated channels were approximately 1,850 µm deep, which significantly increased topical MAL-induced porphyrin fluorescence (hair follicles, dermis, P < 0.0001) and PDT response, both superficially and deep, versus topical MAL application alone. The fraction of porphyrin fluorescence lost by photobleaching was slightly less after 37 J/cm(2) than after 200 J/cm(2) (overall median values 67-90%; 37 vs. 200 J/cm(2), P > 0.05 for all but one comparison). Photobleaching was steady throughout skin layers and did not vary significantly with skin depth at either LED fluence (P > 0.05). CONCLUSIONS: AFR greatly facilitates topical MAL-induced porphyrins and the fraction of photobleached porphyrins is similar for superficial and deep skin. These observations are consistent with AFR-enhanced uptake of MAL, increased porphyrin synthesis, and photodynamic activation of deep porphyrins even at the lower fluence of 37 J/cm(2), widely used in clinical practice. AFR appears to be a clinically practical means for improving PDT deep into the skin. Clinical studies are suggested to evaluate selectivity in targeting dysplastic cell types.