Liposome-encapsulated 3H-5FU in rabbits

We compared the pharmacokinetics of liposome-encapsulated tritiated 5-fluorouracil (3H-5FU-Lipo) to 3H-5FU in buffered saline (3H-5FU-PBS) after subconjunctival or intravitreal injection into rabbit eyes. Liposomes were prepared using phosphatidylcholine, phosphatidic acid, and alpha-tocopherol. Following a unilateral subconjunctival injection of either 3H-5FU-Lipo or 3H-5FU-PBS, rabbits were sacrificed at 0.5, 1, 4, and 8 hours. Significantly higher (p less than 0.05) drug levels were achieved with the encapsulated drug in the vitreous at all four time points and in the aqueous at three of four time points. Following bilateral intravitreal injections of 500 micrograms of 5FU in 0.1 ml, as either 3H-5FU-Lipo or 3H-5FU-PBS injected rabbits were sacrificed at 0, 6, 12, 24, and 48 hours. Vitreal drug levels were significantly higher (p less than 0.05) with encapsulated drug at all time points from 6 hours on. At 48 hours, the vitreal level with the encapsulated drug was 578 +/- 0.23 micrograms/ml compared with 1.06 +/- 0.07 micrograms/ml for 3H-5FU-PBS.