title: In vitro and in vivo studies evaluating a liposome system for drug solubilization.
abstract: A liposome system was developed which demonstrates suitability as an intravenous drug carrier for a lipophilic drug compound (RS-93522, a dihydropyridine CA2+ channel blocker). An aqueous phospholipid suspension was employed as a nontoxic solubilizing vehicle for this drug. The liposome formulation, composed of a 3% mixture of dioleoylphosphatidylcholine and dioleoylphosphatidylglycerol, produced a physically and chemically stable preparation which solubilized the lipophilic drug compound at a concentration 500 times above its intrinsic aqueous solubility. Characterizing the liposome-drug system by gel filtration chromatography showed that the drug comigrated with the lipid constituents of the liposome. Further in vitro studies established that the liposome-RS-93522 formulation allowed for rapid and complete transfer of the drug from the liposome to bind with albumin when added to human serum. In vivo studies with rats were performed in which the pharmacokinetics of the liposomal-RS-93522 system were compared to those of a cosolvent-solubilized RS-93522 solution. This study showed that the pharmacokinetic profiles of the two solutions were identical. All the evidence indicates that a liposome formulation of this type does not alter the distribution of the drug in serum and is, therefore, not likely to affect the intrinsic pharmacological or toxicological parameters of the drug relative to the conventional solvent/excipient-containing formulation. This liposome system demonstrates utility as a biocompatible, nontoxic drug delivery vehicle.
authors.affiliation: Institute of Pharmaceutical Science, Syntex Research, Palo Alto, California 94304.
authors.forename: D M
authors.initials: DM
authors.lastname: Lidgate
authors.forename: P L
authors.initials: PL
authors.lastname: Felgner
authors.forename: J S
authors.initials: JS
authors.lastname: Fleitman
authors.forename: J
authors.initials: J
authors.lastname: Whatley
authors.forename: R C
authors.initials: RC
authors.lastname: Fu
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology; D004337:Drug Carriers; D008081:Liposomes; D008297:Male; D010316:Particle Size; D010743:Phospholipids; D051381:Rats; D011919:Rats, Inbred Strains; D012588:Scintillation Counting; D012709:Serum Albumin / Q000378:metabolism; D012995:Solubility
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004337:Drug Carriers; D008081:Liposomes; D010743:Phospholipids; D012709:Serum Albumin; C059331:RS 93522-004