Abstract | BACKGROUND: Light fractionation significantly increases the efficacy of 5-aminolevulinic acid (ALA) based photodynamic therapy ( PDT) using the nano- emulsion based gel formulation BF-200. PDT using BF-200 ALA has recently been clinically approved and is under investigation in several phase III trials for the treatment of actinic keratosis. This study is the first to compare BF-200 ALA with ALA in preclinical models. RESULTS: In hairless mouse skin there is no difference in the temporal and spatial distribution of protoporphyrin IX determined by superficial imaging and fluorescence microscopy in frozen sections. In the skin-fold chamber model, BF-200 ALA leads to more PpIX fluorescence at depth in the skin compared to ALA suggesting an enhanced penetration of BF-200 ALA. Light fractionated PDT after BF-200 ALA application results in significantly more visual skin damage following PDT compared to a single illumination. Both ALA formulations show the same visual skin damage, rate of photobleaching and change in vascular volume immediately after PDT. Fluorescence immunohistochemical imaging shows loss of VE-cadherin in the vasculature at day 1 post PDT which is greater after BF-200 ALA compared to ALA and more profound after light fractionation compared to a single illumination. DISCUSSION:
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Authors | Henriëtte S de Bruijn, Sander Brooks, Angélique van der Ploeg-van den Heuvel, Timo L M Ten Hagen, Ellen R M de Haas, Dominic J Robinson |
Journal | PloS one
(PLoS One)
Vol. 11
Issue 2
Pg. e0148850
( 2016)
ISSN: 1932-6203 [Electronic] United States |
PMID | 26872051
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- BF-200 ALA
- Photosensitizing Agents
- Protoporphyrins
- Aminolevulinic Acid
- protoporphyrin IX
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Topics |
- Aminolevulinic Acid
(analogs & derivatives, pharmacokinetics, pharmacology)
- Animals
- Animals, Outbred Strains
- Dose Fractionation, Radiation
- Drug Evaluation, Preclinical
- Endothelial Cells
(metabolism)
- Female
- Mice
- Microscopy, Fluorescence
- Photochemotherapy
(methods)
- Photosensitizing Agents
(pharmacokinetics, pharmacology)
- Protoporphyrins
(pharmacokinetics)
- Skin
(blood supply, drug effects, metabolism)
- Sus scrofa
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