Effect of vehicles and esterification on the penetration and distribution of hypericin in the skin of hairless mice

SummaryTo 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 4 h. 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.