title: Comparison of liposome-encapsulated acyclovir with acyclovir ointment: ocular pharmacokinetics in rabbits.
abstract: A positively charged liposomal formulation for topical administration of acyclovir (ACV) was investigated in comparison with a commercial ACV ointment, by determining the pharmacokinetic profile of the drug in the aqueous humor of rabbits after topical administration. The ointment was tested at two different strengths: undiluted (3.0%) and diluted to the same ACV concentration as the liposomal vehicle (0.12%). A liquid formulation containing ACV plus "empty" liposomes and an isotonic aqueous ACV solution were also tested. The applied ACV dose was 0.18 mg, except for the full-strength (3.0%) ointment, in which case it was 1.5 mg. The ACV liposomal dispersion (LIPO-ACV) produced a significantly higher drug concentration profile in the aqueous with respect the three reference formulations containing the same ACV concentration, and showed a 90-minute plateau. The aqueous humor ACV concentration maintained by LIPO-ACV during the plateau was in the upper range of the ID(50)s (0.01 to 0.7 microg/mL) reported for Herpes simplex type 1. In spite of the much higher dose (1.5 versus 0.18 mg), the area under curve (AUC) produced by the full-strength 3.0% ointment was only 1.6 times greater than that corresponding to the liposomal vehicle. In vitro release tests through a cellophane membrane substantiated the concept that positively charged liposomal formulations owe their efficacy to interactions with the positively charged corneal epithelium.
authors.affiliation: Department of Bioorganic Chemistry and Biopharmaceutics, University of Pisa, Pisa, Italy. chetonip@farm.unipi.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Chetoni
authors.forename: Sara
authors.initials: S
authors.lastname: Rossi
authors.forename: Susi
authors.initials: S
authors.lastname: Burgalassi
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.forename: Silvia
authors.initials: S
authors.lastname: Mariotti
authors.forename: M Fabrizio
authors.initials: MF
authors.lastname: Saettone
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000287:Administration, Topical; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001082:Aqueous Humor / Q000378:metabolism*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D008081:Liposomes; D008297:Male; D009824:Ointments; D011817:Rabbits; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D008081:Liposomes; D009824:Ointments; D000212:Acyclovir