R-[N-acetyl]eglin c:poly(oxyethylene) conjugates: preparation, plasma persistence, and urinary excretion.
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 c:POE). 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 c:POE 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.
Goddard
P
P
Advanced Drug Delivery Research Unit, Ciba-Geigy Pharmaceuticals, Horsham, West Sussex, U.K.
O'Mullane
J
J
Ambler
L
L
Daw
A
A
Brookman
L
L
Lee
A
A
Petrak
K
K
D000595:Amino Acid Sequence; D000818:Animals; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000302:isolation & purification; D011506:Proteins; D015842:Serine Proteinase Inhibitors / Q000097:blood / Q000737:chemistry* / Q000302:isolation & purification / Q000652:urine; D015843:Serpins
D007457:Iodine Radioisotopes; D011506:Proteins; D015842:Serine Proteinase Inhibitors; D015843:Serpins; C028656:eglin proteinase inhibitors; D011092:Polyethylene Glycols; D010196:Pancreatic Elastase