ABSTRACT
Hypericin is a photo-active dye originating from the St. John's wort. Two patients with disseminated superficial actinic porokeratosis (DSAP) were treated with photodynamic therapy (PDT) using topical hypericin. Although a partial response was obtained in one patient topical hypericin-PDT does not emerge as a promising treatment for DSAP.
Subject(s)
Perylene/analogs & derivatives , Photochemotherapy , Porokeratosis/radiotherapy , Administration, Topical , Aged , Anthracenes , Antineoplastic Agents/therapeutic use , Female , Humans , Middle Aged , Perylene/therapeutic useABSTRACT
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.
Subject(s)
Neoplasms, Radiation-Induced/physiopathology , Perylene/analogs & derivatives , Skin Absorption , Skin Neoplasms/physiopathology , Skin/metabolism , Ultraviolet Rays/adverse effects , Administration, Topical , Animals , Anthracenes , Female , Fluorescence , Mice , Mice, Hairless , Perylene/administration & dosage , Perylene/pharmacokinetics , PhotochemotherapyABSTRACT
To study the in vivo penetration and skin distribution of hypericin, the compound (0.1%) was formulated in 10 different vehicles that are commonly used in pharmaceutical compounding, and applied on the skin of hairless mice for 4h. After application of hypericin in PEG ointment, white petrolatum or unguentum emulsificans, fluomicroscopic analysis of skin sections revealed penetration to be confined to the stratum corneum. On the contrary, Beeler base, unguentum sorbatis 100 and cremor non ionicus caused penetration of hypericin in the viable epidermis. To reduce the prominent depot formation in the stratum corneum, which was observed irrespectively of the formulation applied, hypericin was esterified into its hydrolyzable acetate derivative. The influence of esterification proved to be substantial when hypericin acetate (0.15%) was incorporated in unguentum sorbatis 100, as hypericin-related fluorescence could be detected deeply within the dermis. Moreover, accumulation in the sebaceous glands was found to be prominent. These results indicate the value of further studies regarding the application of hypericin and hypericin acetate as topical photosensitizers for photodynamic therapy.
