Effect of Topically Applied -Aminopropionitrile on Granuloma Tissue Biochemistry

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Abstract
The effects of the percutaneous transport of vehicles and the transport of .beta.-amino-propionitrile (.beta.APN) in vehicles were studied in rats. The bioavailability of topically administered .beta.APN was determined by measuring the degree of collagen cross-linking inhibition in the underlying granuloma tissue. Granulomas were induced by subcutaneous implantation of polyvinylalcohol sponges. From the 4th to 12th days postimplantation, a 20 mg/cm2 dose of .beta.APN fumarate was applied. Vehicles employed included dimethylsulfoxide (DMSO), urea, and occlusion. DMSO significantly enhanced the effect of .beta.APN in reducing the cross-linking of collagen. .beta.APN administered onto urea-pretreated skin and followed by occlusion in the granuloma tissue was more effective than .beta.APN in 30% DMSO, but only in the parameter reflecting extractibility of collagen into urea or thiocyanate solutions. The results suggest that .beta.APN administered topically in an appropriate vehicle penetrates the granuloma tissue and affects collagen polymerization. Though .beta.APN was topically administered, a systemic effect from the drug was evident, as documented by lower body weight of treated rats.