title: Influence of formulation factors on methyl-ALA-induced protoporphyrin IX accumulation in vivo.
abstract: Photodynamic therapy (PDT) is a medical treatment by which a combination of a photosensitising drug and visible light cause the destruction of selected cells. Thick lesions, such as nodular basal cell carcinomas (BCCs), or lesions with overlying keratinous debris, are reported as being difficult to eradicate using 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT). Such treatment failures have been attributed to the shallow penetration of water-soluble drugs like ALA. In addition, the current scarcity of sophisticated drug delivery research centered on PDT applications has meant that accurate comparison of similar clinical studies is difficult. This paper investigates, for the first time, novel drug delivery systems for controlled drug delivery of methyl-ALA (M-ALA). Pressure sensitive adhesive (PSA) and bioadhesive patches containing defined M-ALA loadings and a standard cream containing equivalent amounts of drug were applied to the skin of mice for defined periods of time and the fluorescence of the protoporphyrin IX (PpIX) induced measured over 24h. Of major importance, the PSA patches containing low drug loadings induced high PpIX levels, which were limited to the site of application, after only 1h applications. Such systems have the potential to improve selectivity of PpIX accumulation, increase simplicity of treatment and, due to the low drug loadings required, reduce costs of clinical PDT. PSA patches would be most suitable for application to areas of dry skin, while bioadhesive patches would be suitable for moist areas, such as the mouth or lower female reproductive tract and have been shown here to induce significant PpIX production at the site of application after 4h applications of patches containing high drug loadings.
authors: School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK; Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello 0310, Oslo, Norway.
authors: Ryan F
authors: RF
authors: Donnelly
authors: Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello 0310, Oslo, Norway; Fellow of the Norwegian Cancer Society, P.O. Box 4 Sentrum 0101, Oslo, Norway.
authors: Petras
authors: P
authors: Juzenas
authors: School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors: Paul A
authors: PA
authors: McCarron
authors: Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello 0310, Oslo, Norway.
authors: Li-Wei
authors: LW
authors: Ma
authors: School of Pharmacy, Queens University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors: A David
authors: AD
authors: Woolfson
authors: Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello 0310, Oslo, Norway; Institute of Physics, University of Oslo, P.O. Box 1048 Blindern 0316, Oslo, Norway.
authors: Johan
authors: J
authors: Moan