Abstract
AbstractLiposomal delivery of phosphonoformate (PF), an antiviral agent with poor membrane permeability, was evaluated using a passive targeting strategy to treat Rauscher murine leukemia virus (RMLV) infection. Pharmacokinetic studies in RMLV infected mice using the nonmetabolized [14C]PF reveal that nonencapsulated PF is rapidly excreted with an approximate clearance of 18.8 g blood/hour, while liposome (egg phos-phatidylcholine/egg phosphatidylglycerol/cholesterol: 9:1:8)-encapsulated PF has an approximate clearance of 0.61–0.96 g blood/hr. When administered in the liposome encapsulated form, 50–80% of the dose is found in the liver, spleen, and blood at 3 hr postinjection. The area under the drug level-time curve (AUC) in the liver and spleen following a single dose of encapsulated PF is 1.3–1.7 times higher than the AUC of a 25-fold larger dose of nonencapsulated PF. Biodistribution studies of 125I-labeled liposomes or encapsulated [14C]PF in vivo show that the specific uptake of liposomes and entrap...
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