Pretreatment with ablative fractional laser changes kinetics and biodistribution of topical 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL).
OBJECTIVE
5-Aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) are porphyrin precursors used topically for photodynamic therapy (PDT). Previous studies have established that ablative fractional laser (AFXL) increases topical drug uptake. We evaluated kinetics and biodistribution of ALA- and MAL-induced porphyrins on intact and disrupted skin due to AFXL.


METHODS
Two Yorkshire swine were exposed to CO2 AFXL (10.6 µm, 1,850 µm ablation depth) and subsequent topical application of ALA and MAL cream formulations (20%, weight/weight). Porphyrin fluorescence was quantified by digital fluorescence photography (30, 90, and 180 minutes) and fluorescence microscopy at specific skin depths (180 minutes).


RESULTS
Porphyrins gradually formed over time, differently on intact and AFXL-disrupted skin. On intact skin (no AFXL), fluorescence photography showed that MAL initially induced higher fluorescence than ALA (t = 30 minutes MAL 21.1 vs. ALA 7.7 au, t = 90 minutes MAL 39.0 vs. ALA 26.6 (P < 0.009)) but reached similar intensities for long-term applications (t = 180 minutes MAL 56.6 vs. ALA 52 au, P = ns). AFXL considerably enhanced porphyrin fluorescence from both photosensitizers (P < 0.05). On AFXL-exposed skin, MAL expressed higher fluorescence than ALA for short-term application (t = 30 minutes, AFXL-MAL 26.4 vs. AFXL-ALA 14.1 au, P < 0.001), whereas ALA over time overcame MAL and induced the highest fluorescence intensities obtained (t = 180 minutes, AFXL-MAL 98.6 vs. AFXL-ALA 112.0 au, P < 0.001). In deep skin layers, fluorescence microscopy showed higher fluorescence in hair follicle epithelium for ALA than MAL (t = 180 minutes, 1.8 mm, AFXL-MAL 35.3 vs. AFXL-ALA 46.7 au, P < 0.05).


CONCLUSIONS
AFXL changes kinetics and biodistribution of ALA and MAL. It appears that AFXL-ALA favors targeting deep structures.
Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, 02114; Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, 2400, Denmark.
Merete
M
Haedersdal
Fernanda H
FH
Sakamoto
William A
WA
Farinelli
Apostolos G
AG
Doukas
Joshua
J
Tam
R Rox
RR
Anderson
D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000818:Animals; D054020:Lasers, Gas; D008856:Microscopy, Fluorescence; D010781:Photography; D011166:Porphyrins / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects*; D012869:Skin Absorption; D013552:Swine; D014018:Tissue Distribution
D011166:Porphyrins; C475457:methyl 5-aminolevulinate; D000622:Aminolevulinic Acid
ablative fractional laser; drug delivery; fluorescence microscopy; fluorescence photography; protoporphyrin IX