Skin photosensitization with topical hypericin in hairless mice.
Hypericin, a naturally occurring photosensitizer, exhibits interesting in vitro photobiological activities, which suggest that the compound is a potential antipsoriatic agent. In this study, the possibility of hypericin penetrating the skin in photo-active concentrations has been studied. Hypericin is incorporated in either emulsifying ointment supplemented with solketal (hypericin content: 0.05%) or in polyethylene glycol (PEG) ointment (hypericin content: 0.5%) and applied to the skin of hairless mice for 4 h. After removing excess ointment, the mice are then irradiated with different light doses using a 500 W halogen lamp. As a positive control, intraperitoneally (i.p.) administered hypericin (10 and 40 mg/kg) has also been tested. Erythema, desquamation and erosions are demonstrated in the mice treated with hypericin in emulsifying ointment with solketal using a light dose of at least 4.5 J/cm2. In general, these reactions correlate well with those of i.p. administered hypericin (40 mg/kg), indicating that hypericin incorporated in emulsifying ointment with solketal is well absorbed by the skin of the mice. However, for the i.p. administered hypericin (40 mg/kg), we could not evaluate phototoxic reactions in the group of animals that received a light dose of 108 J/cm2, as they all died 12-24 h after irradiation, indicating extreme photosensitization with systemic hypericin at higher light doses. On the contrary, there is no measurable skin photosensitivity induced by hypericin when incorporated in PEG ointment or when 10 mg/kg hypericin is i.p. administered. Our results show that hypericin incorporated in a suitable vehicle can be delivered to the skin in photo-active concentrations. Using a vehicle such as emulsifying ointment with solketal, it will be possible to explore the photo-activity of hypericin in the treatment of psoriasis and other skin diseases.
Kamuhabwa
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AR
Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Belgium.
Roelandts
R
R
de Witte
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PA
D000287:Administration, Topical; D000818:Animals; D000873:Anthracenes; D007274:Injections, Intraperitoneal; D051379:Mice; D008812:Mice, Hairless; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011092:Polyethylene Glycols; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects*
D000873:Anthracenes; D011838:Radiation-Sensitizing Agents; D011092:Polyethylene Glycols; D010569:Perylene; C004965:hypericin