title: Influence of application and formulation factors on the penetration of hypericin in normal mouse skin and UV induced skin tumors.
abstract: Hypericin, a naturally occurring photosensitizer, is currently being investigated for topical use in photodynamic therapy (PDT). In a previous study, it was found that hypericin can be delivered in the epidermis of hairless mouse skin after a 4-h application in Beeler base. With the intention to further optimize the penetration conditions, the present study examines the effect of the concentration of hypericin in the cream, the application time, the presence of penetration enhancers and occlusion on the penetration of hypericin in the skin of hairless mice. Experiments with different hypericin concentrations and application times indicated that application of 0.1% hypericin for 12-24 h maximizes the accumulation of hypericin-related fluorescence in the skin, as estimated by fluorescence microscopy with image analysis. Depending on the formulation, the use of an occlusive dressing did not alter, or even reduced the accumulation of hypericin in the viable layers. Also, the addition of propylene glycol (30%) and oleic acid (5%) did not change hypericin fluorescence levels in the epidermis. Conversely, incorporation of ethanol (40%, integrated in a gel, and added to Beeler base) increased dramatically the fluorescence levels in all skin layers. Consequently, the optimized conditions were used to investigate the penetration of hypericin into UV induced skin tumors. It was found that application under occlusion of hypericin, formulated in the gelcream containing ethanol, during 24 h enabled the penetration of hypericin in the entire skin lesions with a relatively homogenous distribution. In conclusion, our results suggest the possible use of 0.1% hypericin in a gelcream containing ethanol for PDT of skin lesions.
authors.affiliation: Laboratory for Pharmaceutical Biology, Faculty of Pharmaceutical Sciences, K.U. Leuven, Herestraat 49, Box 824, B-3000 Leuven, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Boiy
authors.forename: Rik
authors.initials: R
authors.lastname: Roelandts
authors.forename: Peter A M
authors.initials: PA
authors.lastname: de Witte
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000873:Anthracenes; D005260:Female; D005453:Fluorescence; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000503:physiopathology*; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D010778:Photochemotherapy; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D012878:Skin Neoplasms / Q000503:physiopathology*; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000873:Anthracenes; D010569:Perylene; C004965:hypericin