Porphyrin distribution after topical aminolevulinic acid in a novel porcine model of sebaceous skin.
OBJECTIVE
Aminolevulinic acid photodynamic therapy (ALA-PDT) depends on drug metabolism into porphyrins. Clinically, ALA-PDT has been used with a wide range of protocols for treating both epidermal and dermal targets, despite limited understanding of porphyrin biodistribution over time. We studied porphyrin accumulation after topical application of ALA in vivo, and also describe the porcine ear as a new animal model to study adnexal glands.


METHODS
The microanatomy of anterior ear skin of swine was measured. Topical 20% ALA in water/ethanol was applied under occlusion. Biopsies taken after 5, 10, 15, and then every 15 minutes for a total of 3 hours were examined by fluorescence microscopy of frozen sections to assess accumulation and distribution of porphyrins.


RESULTS
Porphyrin fluorescence of digital photomicrograph images was not visually apparent until 30-45 minutes after application, although quantitative pixel analysis showed a statistically significant increase in epidermal fluorescence only 15 minutes after ALA application. From 30 to 120 minutes, epidermis, hair follicles (HF), and sebaceous glands (SG) became progressively more fluorescent. Eccrine gland fluorescence began to be detected after 30 minutes; SG showed fluorescence starting at 45-75 minutes. Fluorescence in all sites reached maximum intensity from 75 to 180 minutes of incubation. There was a trend for HF and SG to express stronger fluorescence compared with epidermis and eccrine glands.


CONCLUSIONS
Anterior pig ear skin is microanatomically similar to human sebaceous skin. The time-dependent accumulation of porphyrins in pilosebaceous units and eccrine glands in this model suggests other routes of uptake of topical ALA in addition to the trans-epidermal route. Apparently, time interval between ALA application and light exposure could be optimized for different uses of ALA-PDT.
Sakamoto
Fernanda H
FH
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Tannous
Zeina
Z
Doukas
Apostolos G
AG
Farinelli
William A
WA
Smith
Nicholas A
NA
Zurakowski
David
D
Anderson
R Rox
RR
D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage*; D000818:Animals; D005260:Female; D023421:Models, Animal; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D011166:Porphyrins / Q000493:pharmacokinetics*; D012627:Sebaceous Glands / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D013552:Swine; D014018:Tissue Distribution
D017319:Photosensitizing Agents; D011166:Porphyrins; D000622:Aminolevulinic Acid