title: Poloxamer 407-mediated changes in plasma cholesterol and triglycerides following intraperitoneal injection to rats.
abstract: Poloxamer (Pluronic) nonionic surfactant vehicles are a series of chemically-related block copolymers finding widespread use in parenteral formulations as solubilizing and wetting agents for traditional, low-molecular weight organic drug molecules, as well as stabilizing agents for proteins and polypeptide drugs. We report the effects of poloxamer 407 (Pluronic F-127) on plasma cholesterol and triglyceride concentrations in rats. Poloxamer 407 injected into rats by intraperitoneal injection (dose = 1.5 gm/kg) resulted in sustained (greater than 96 hour) hypercholesterolemia and hypertriglyceridemia. A larger dose of poloxamer 407 was required to elevate plasma triglyceride relative to total cholesterol. Ingestion of commercial rat chow had a negligible effect on plasma cholesterol and triglycerides levels in control (no poloxamer injection) animals, but consumption of food by animals that received an intraperitoneal injection of poloxamer 407 (30% w/w) resulted in significantly (p < .05) greater elevations in plasma cholesterol and triglycerides than in fasted animals administered poloxamer 407. The route of poloxamer 407 administration, namely intramuscular vs. intraperitoneal injection, was observed to be a more important factor for poloxamer-induced elevations in plasma cholesterol than poloxamer-mediated elevations in plasma triglycerides. Our results also provide suggestive evidence that the mechanism responsible for the elevation of plasma cholesterol following intraperitoneal injection of a poloxamer 407 solution (30% w/w) to rats may be due to stimulation of 3-hydroxy-3-methylglutaryl-co-enzyme A (HMG-CoA) reductase activity in the liver by the poloxamer vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)
authors: Department of Pharmaceutics, College of Pharmacy, University of Illinois, Chicago.
authors: Z G
authors: ZG
authors: Wout
authors: E A
authors: EA
authors: Pec
authors: J A
authors: JA
authors: Maggiore
authors: R H
authors: RH
authors: Williams
authors: P
authors: P
authors: Palicharla
authors: T P
authors: TP
authors: Johnston
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood*; D004195:Disease Models, Animal; D006937:Hypercholesterolemia / Q000139:chemically induced*; D015228:Hypertriglyceridemia / Q000139:chemically induced*; D007274:Injections, Intraperitoneal; D008297:Male; D011060:Poloxalene; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood*
chemical_list: D014280:Triglycerides; D011060:Poloxalene; D002784:Cholesterol