Determination and pharmacokinetic profile of liposomal foscarnet in rabbit ocular tissues after intravitreal administration

Abstract

The treatment of ocular diseases affecting the posterior segment of the eye, such as cytomegalovirus (CMV) retinitis, requires the access of the drugs to the vitreous humor. Foscarnet inhibits replication of herpesviruses, including CMV. The drug's encapsulation in liposomes is meant not only to increase activity and to prolong the effect of the drug, but also to reduce its toxicity. The aims of the present study were to evaluate foscarnet levels and its pharmacokinetic parameters in vitreous humor and retinal tissue of rabbits after the administration of an intravitreal injection of both liposomal foscarnet and foscarnet commercial solution. Liposomes were prepared by the reverse-phase evaporation method. The amount of encapsulated foscarnet (F) was 63% wt. The in vitro diffusion assays showed that F was released more slowly when formulated in liposomes than in the commercial solution. The in vivo studies showed that, as opposed to commercial solution F, liposomal F achieves stable and durable therapeutic levels in retina, going beyond 72h, reaching the vitreous humor with adequate levels to accomplish the aims of intravitreal therapy. Lyophilization also increased stability and dispersion of liposomes in aqueous medium, although not improving the pharmacokinetic results over those from non-lyophilized liposomes.