Physical model evaluation of topical prodrug delivery--simultaneous transport and bioconversion of vidarabine-5'-valerate IV: Distribution of esterase and deaminase enzymes in hairless mouse skin

Abstract

A semiquantitative assessment of estrase and deaminase distributions in hairless mouse skin was performed in vitro. The enzyme activities were quantified using 3H-vidarabine and tis 5'-valerate as the substrates. Full-thickness skin of the hairless mouse was cut into two halves, and each half was homogenized in pH 7.4 buffer. BQOTH THE SUPERNATE AND THE RESIDUE OF THE HOMOGENATE were assayed for esterase and deaminase activities. Results show that the outer half-thickness of the skin contained more esterase but slightly less deaminase than the other half. The characteristics of the esterase and the deaminase reactions also were studied employing the crude enzyme extract; these reactions were essentially irreversible. The deaminase reaction was in the linear region of Michaelis-Menten kinetics for substrate concentrations up to 4.5 x 10(-5) M.