title: Release kinetics of liposome-encapsulated ganciclovir after intravitreal injection in rabbits.
abstract: This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped ganciclovir could prolong intraocular therapeutic levels when it is compared to the intravitreal injection of a simple solution of the drug. New Zealand white rabbits were given an intravitreal injection of the drug solution and of liposome-encapsulated ganciclovir. The intravitreal clearance of ganciclovir was determined after a single injection of either the drug solution (200 micrograms/0.1 mL) or the liposomally-entrapped (with 41% load; 82 micrograms drug load and 118 micrograms free) ganciclovir. The ganciclovir vitreal concentrations were measured at various time intervals for a period up to 43 days using an HPLC method. The results of this study clearly demonstrated that prolonged intravitreal drug levels (above the mean inhibitory dose of cytomegalovirus of 1 microgram/mL) after administration of the liposome-entrapped ganciclovir and estimated to continue beyond 30-43 days. The injection of the 200 micrograms/0.1 mL of drug solution showed a mean vitreous concentration which was higher than the ID50 only for 55 h. The disappearance rate constant for the liposome-encapsulated injections was approximately 22 x slower than simple drug solution injections (controls). No evidence of retinal toxicity was found by clinical or light microscopy examination of the treated eyes.
authors.affiliation: Laboratoire de Pharmacie galénique, Faculté de Pharmacie, Université de Rennes, France.
authors.forename: C
authors.initials: C
authors.lastname: Le Bourlais
authors.forename: F
authors.initials: F
authors.lastname: Chevanne
authors.forename: P
authors.initials: P
authors.lastname: Ropert
authors.forename: G
authors.initials: G
authors.lastname: Bretagne
authors.forename: L
authors.initials: L
authors.lastname: Acar
authors.forename: H
authors.initials: H
authors.lastname: Zia
authors.forename: P A
authors.initials: PA
authors.lastname: Sado
authors.forename: T
authors.initials: T
authors.lastname: Needham
authors.forename: R
authors.initials: R
authors.lastname: Leverge
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D015774:Ganciclovir / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics*; D006207:Half-Life; D007267:Injections; D008081:Liposomes; D008297:Male; D008854:Microscopy, Electron; D010316:Particle Size; D011817:Rabbits; D012996:Solutions; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D008081:Liposomes; D012996:Solutions; D015774:Ganciclovir