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

TY - JOUR

T1 - Enhanced uptake and photoactivation of topical methyl aminolevulinate after fractional CO2 laser pretreatment

AU - Haedersdal, M

AU - Katsnelson, J

AU - Sakamoto, F H

AU - Farinelli, W A

AU - Doukas, A G

AU - Tam, J

AU - Anderson, R R

N1 - Copyright © 2011 Wiley-Liss, Inc.

PY - 2011/9

Y1 - 2011/9

N2 - 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 3milliseconds, 91.6mJ per pulse and subsequent topical MAL application for 3hours (Metvix®). Red light (LED arrays) was then delivered at fluences of 37 and 200J/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 1,800μm. Results Laser-ablated channels were approximately 1,850μm 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 37J/cm 2 than after 200J/cm 2 (overall median values 67-90%; 37 vs. 200J/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 37J/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.

AB - 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 3milliseconds, 91.6mJ per pulse and subsequent topical MAL application for 3hours (Metvix®). Red light (LED arrays) was then delivered at fluences of 37 and 200J/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 1,800μm. Results Laser-ablated channels were approximately 1,850μm 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 37J/cm 2 than after 200J/cm 2 (overall median values 67-90%; 37 vs. 200J/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 37J/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.

U2 - 10.1002/lsm.21096

DO - 10.1002/lsm.21096

M3 - Journal article

SN - 0196-8092

VL - 43

SP - 804

EP - 813

JO - Lasers in Surgery and Medicine

JF - Lasers in Surgery and Medicine

IS - 8

ER -