In photodynamic therapy with topically applied delta-aminolevulinic acid porphyrins are acting as photosensitizers. The profile of porphyrin metabolites in normal or in neoplastic skin after administration of delta-aminolevulinic acid has not been determined in detail yet. Thus, to study porphyrin biosynthesis in human skin an organ culture model was developed. Explant pieces of normal skin, keratoacanthoma, and basal cell carcinoma were incubated with 1 mM delta-aminolevulinic acid for 36 h. Levels of delta-aminolevulinic acid, porphyrins and porphyrin metabolites were measured in tissues and supernatants. After incubation with delta-aminolevulinic acid, higher porphyrin levels were demonstrated in tumors as compared to normal skin. In supernatants, most of formed porphyrins, preferentially highly carboxylated porphyrin metabolites, were measured. The pattern of synthesized porphyrins differed between normal and neoplastic skin explants. In tissues of basal cell carcinomas protoporphyrin was preferentially shown and tissues of keratoacanthomas were characterized by a predominance of coproporphyrin as compared to normal skin. The results show that explant cultures offer an easy approach to examine the porphyrin biosynthesis of various tissues. The tumor-specific delta-aminolevulinic acid metabolism indicates additional porphyrin metabolites such as coproporphyrin apart from protoporphyrin as effective photosensitizers and may offer a novel approach to tumor-selective photodynamic damage.

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In a bilateral paired comparison (randomized double-blind study) 31 dermatitis patients (atopic and contact dermatitis) were tested with two ointments containing 0.0056% betamethasone-17-benzoate. One ointment was applied on each side of the body. The topical formulations differed in their solution capacities for the drug by a factor of about 50 (solution-type: high mutual affinity between drug and vehicle; suspension-type: low affinity). The different antiinflammatory effects were studied visually by assessing five symptoms: erythema, scaling, infiltration, lichenification, and excoriation. On the 5th day, 73% of the patients showed significant differences between the sides in favor of the suspension-type ointment (Wilcoxon test). Blanching tests on 30 volunteers confirmed the result. The in vitro drug release, however, was faster with the solution-type ointment. The efficacy of an ointment can be increased greatly, if the solution capacity for the drug is low, and thus the partition coefficient between the stratum corneum (barrier of the skin) and the vehicle is high. As long as the barrier is not damaged completely, the difference in drug release is not the determining factor for the effect.

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