The impact of treatment density and molecular weight for fractional laser-assisted drug delivery.

Ablative fractional lasers (AFXL) facilitate uptake of topically applied drugs by creating narrow open micro-channels into the skin, but there is limited information on optimal laser settings for delivery of specific molecules. The objective of this study was to investigate the impact of laser treatment density (% of skin occupied by channels) and molecular weight (MW) for fractional CO(2) laser-assisted drug delivery. AFXL substantially increased intra- and transcutaneous delivery of polyethylene glycols (PEGs) in a MW range from 240 to 4300 Da (Nuclear Magnetic Resonance, p<0.01). Increasing laser density from 1 to 20% resulted in augmented intra- and transdermal delivery (p<0.01), but densities higher than 1% resulted in reduced delivery per channel. Mass spectrometry indicated that larger molecules have greater intracutaneous retention than transcutaneous penetration. At 5% density, median delivery of PEGs with mean MW of 400, 1000, 2050 and 3350 Da were respectively 0.87, 0.31, 0.23 and 0.15 mg intracutaneously and 0.72, 0.20. 0.08 and 0.03 mg transcutaneously, giving a 5.8- and 24.0-fold higher intra- and transcutaneous delivery of PEG400 than PEG3350 (p<0.01). This study substantiates that fractional CO(2) laser treatment allows uptake of small and large molecules into and through human skin, and that laser density can be varied to optimize intracutaneous or transcutaneous delivery.