R-[N-acetyl]eglin c:poly(oxyethylene) conjugates: preparation, plasma persistence, and urinary excretion.

ABSTRACT

In this paper, we describe the preparation, purification, and characterization of conjugates of R-[N-acetyl]eglin c (Eglin c) with poly(oxyethylene) (POE; Eglin cPOE). The plasma profile and urinary excretion of the conjugates has been determined after iv administration in mice. The modification of Eglin c with POE does not significantly impair the ability of Eglin c to bind elastase as measured by an in vitro assay. In the best example, 79% of theoretical activity was retained by the conjugate. The in vivo results clearly show that the amount of Eglin cPOE in plasma after iv administration is much higher than comparative doses of unconjugated Eglin c. The time course of the plasma concentration of the conjugate matches closely that of the corresponding free polymer. Consequently, we can expect that higher plasma concentration could be achieved, if and when required, by selecting polymers of appropriate size.