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 mug/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.
Comparison of Liposome-Encapsulated Acyclovir with Acyclovir Ointment: ocular pharmacokinetics in rabbits
CHETONI, PATRIZIA;BURGALASSI, SUSI;MONTI, DANIELA;
2004-01-01
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 mug/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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
