Document Detail


Autoradiographic and scintillation analysis of 5-aminolevulinic acid permeation through epithelialised tissue: implications for topical photodynamic therapy of superficial gynaecological neoplasias.
MedLine Citation:
PMID:  17657596     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: 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. MATERIALS AND 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.
Authors:
Paul A McCarron; Ryan F Donnelly; A David Woolfson
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Publication Detail:
Type:  Journal Article     Date:  2007-07-27
Journal Detail:
Title:  Pharmaceutical research     Volume:  25     ISSN:  0724-8741     ISO Abbreviation:  Pharm. Res.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-04-03     Completed Date:  2008-08-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  812-26     Citation Subset:  IM    
Affiliation:
School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast, BT9 7BL, UK. p.mccarron@qub.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Administration, Cutaneous
Aminolevulinic Acid / administration & dosage,  chemistry,  metabolism*
Animals
Autoradiography
Chemistry, Pharmaceutical
Diffusion
Dimethyl Sulfoxide / chemistry,  pharmacology
Drug Carriers
Drug Compounding
Epithelial Cells / metabolism
Feasibility Studies
Female
Genital Neoplasms, Female / drug therapy*
Humans
Maleates / chemistry
Ointments
Oleic Acid / chemistry,  pharmacology
Permeability
Photochemotherapy*
Photosensitizing Agents / administration & dosage,  chemistry,  metabolism*
Polyethylenes / chemistry
Scintillation Counting
Swine
Time Factors
Tissue Adhesives / chemistry
Vagina / drug effects,  metabolism*,  radiography
Chemical
Reg. No./Substance:
0/Drug Carriers; 0/Maleates; 0/Ointments; 0/Photosensitizing Agents; 0/Polyethylenes; 0/Tissue Adhesives; 0/polymethylvinylether-co-maleic anhydride; 106-60-5/Aminolevulinic Acid; 112-80-1/Oleic Acid; 67-68-5/Dimethyl Sulfoxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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