Development of a topical hematoporphyrin derivative formulation: characterization of photosensitizing effects in vivo
Photochemotherapy offers a unique approach for the selective therapy of skin diseases. Hematoporphyrin derivative (HPD) in combination with visible light exhibits cytocidal activity in vitro and systemically has demonstrated applicability to the treatment of experimental and human tumors. This study was undertaken to investigate the phototoxic effects in guinea pig skin of systemic HPD in comparison with locally (intradermal) and topically administered HPD. Maximum erythema was obtained by irradiation with red light or UVA 6 h postsystemic HPD (10 mg/kg). Erythema response was dependent upon the dose of irradiation. Systemic HPD produced complete inhibition of epidermal DNA, RNA, and protein synthesis 6-12 h postirradiation with red light, with a lesser degree of inhibition in the deeper hair roots. Local (intradermal) HPD (5-500 micrograms) in combination with red light or UVA produced a dose-dependent erythema and inhibition of epidermal DNA synthesis. Effective in vitro percutaneous penetration of HPD was demonstrated in vehicles containing Azone and N-methylpyrrolidone. Topical application of these HPD formulations in vivo in combination with red light or UVA produced significant erythema and inhibition of epidermal DNA synthesis. These results suggest that HPD can cause photosensitization of the skin. It may therefore be reasonable to explore topical applications as an alternative approach for the photochemotherapy of psoriasis and other cutaneous diseases.
- Research Organization:
- Univ. of California, Irvine, CA (United States)
- OSTI ID:
- 6747731
- Journal Information:
- J. Invest. Dermatol.; (United States), Vol. 81:6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
HEMATOPORPHYRINS
SYNERGISM
SKIN DISEASES
THERAPY
ULTRAVIOLET RADIATION
VISIBLE RADIATION
BIOLOGICAL EFFECTS
CELL KILLING
ERYTHEMA
GUINEA PIGS
SKIN
ANIMALS
BODY
CARBOXYLIC ACIDS
DISEASES
ELECTROMAGNETIC RADIATION
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
MAMMALS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PIGMENTS
PORPHYRINS
RADIATIONS
RODENTS
SYMPTOMS
VERTEBRATES
560400* - Other Environmental Pollutant Effects