Aminolaevulinic acid diffusion characteristics in 'in vitro' normal human skin and actinic keratosis: implications for topical photodynamic therapy.
BACKGROUND
The response rate of aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) in certain subtypes of actinic keratosis (AK), such as hypertrophic and hyperkeratotic lesions, is variable, an effect attributable to a supposed lack of ALA penetration. A detailed and depth-related profile of spatial ALA permeation in AK following drug administration would lead to a greater understanding of concentrations achievable before protoporphyrin IX biosynthesis and subsequent PDT.


METHODS
ALA penetration through excised normal human skin (NS) and AK lesions was evaluated using a cryostatic sectioning technique and radio-isotope counting following drug delivery using a novel, bioadhesive patch, loaded with 19, 38 or 50 mg/cm(2) ALA.


RESULTS
Distinct differences in ALA concentration with respect to depth between AK and NS samples were shown, particularly within the superficial layers of the tissue structure, down to a depth of 1.0 mm. Patch application times were shown to influence ALA concentrations in tissue, but there was no clear correlation between ALA penetration in AK lesions taken from different body locations and from patients of different age. Similarly, the thickness of stratum corneum was not related to the ALA distribution profiles.


CONCLUSIONS
Sizable variation in ALA concentration was a prominent feature of profiles through AK lesions, which may explain the variation of observed protoporphyrin IX production seen in the clinical implementation of AK PDT. That said, the results of this study show sufficient ALA penetration to a depth of 1.0 mm, which should be satisfactory for successful treatment of the majority of non-hyperkeratotic, hypertrophic AK using patch-based delivery methods.
McLoone
Nabla
N
School of Pharmacy, Medical Biology Centre, Queen's University Belfast, Belfast, UK.
Donnelly
Ryan F
RF
Walsh
Maureen
M
Dolan
Olivia M
OM
McLoone
Sean
S
McKenna
Kevin
K
McCarron
Paul A
PA
D000279:Administration, Cutaneous; D000368:Aged; D000369:Aged, 80 and over; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D002250:Carbon Radioisotopes; D004058:Diffusion; D005260:Female; D016591:Histocytological Preparation Techniques; D006801:Humans; D007642:Keratosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010539:Permeability; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012588:Scintillation Counting; D012867:Skin / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013997:Time Factors; D014466:Ultraviolet Rays / Q000009:adverse effects
D002250:Carbon Radioisotopes; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid