Autoradiographic and scintillation analysis of 5-aminolevulinic acid permeation through epithelialised tissue: implications for topical photodynamic therapy of superficial gynaecological neoplasias.
OBJECTIVE
Aminolevulinic acid (5-ALA) diffusion through both keratinised and non-keratinised tissue, used as a model tissue substrates, was evaluated, together with the depth of permeation and the concentration achieved following delivery from bioadhesive patch and proprietary cream formulations.


METHODS
Moisture-activated, bioadhesive patches loaded with 5-ALA at concentrations of 19.0, 38.0 and 50.0 mg cm(-2) and an o/w cream (20% w/w 5-ALA) were radiolabelled with C14 5-ALA and applied to excised human vaginal tissue and porcine skin. After 1, 2 and 4 h, tissue was sectioned in two orientations and the 5-ALA concentration at specific depths determined using autoradiography and liquid scintillation counting (LSC).


RESULTS
The stratum corneum was a significant barrier to 5-ALA permeation, with concentrations in tissue dependent on application time and drug loading. 5-ALA was detected at 6 mm using autoradiography after 2 h, with LSC showing phototoxic concentrations at 2.375 mm after 4 h of application. Inclusion of oleic acid and dimethyl sulphoxide in bioadhesive patches increased 5-ALA significantly in neonate porcine tissue, but only for patches cast from blends containing 5% w/w oleic acid.


CONCLUSIONS
The bioadhesive patch described delivered 5-ALA to depths of at least 2.5 mm in tissue types indicative of vulval skin, suggesting that photodynamic therapy of deep vulval intraepithelial neoplasia is feasible using this means of bioadhesive 5-ALA delivery.
School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, UK. p.mccarron@qub.ac.uk
Paul A
PA
McCarron
Ryan F
RF
Donnelly
A David
AD
Woolfson
D000279:Administration, Cutaneous; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D004121:Dimethyl Sulfoxide / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers; D004339:Drug Compounding; D004847:Epithelial Cells / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D008298:Maleates / Q000737:chemistry; D009824:Ointments; D019301:Oleic Acid / Q000737:chemistry / Q000494:pharmacology; D010539:Permeability; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D011095:Polyethylenes / Q000737:chemistry; D011859:Radiography; D012588:Scintillation Counting; D013552:Swine; D013997:Time Factors; D014014:Tissue Adhesives / Q000737:chemistry; D014621:Vagina / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*
D004337:Drug Carriers; D008298:Maleates; D009824:Ointments; D017319:Photosensitizing Agents; D011095:Polyethylenes; D014014:Tissue Adhesives; D019301:Oleic Acid; D000622:Aminolevulinic Acid; C043105:poly(methyl vinyl ether-co-maleic anhydride); D004121:Dimethyl Sulfoxide