Objective: To investigate the pharmacokinetic profiles and tissue distribution of long circulating liposome formulations-anionic, cationic, and neutral long circulating liposomes (NA, PA, A-D) in rabbits and mice.
Methods: Conventional liposomes (CA) encapsulated with 125I-bcl-2/bcl-xl ASON and free 125I-bcl-2/bcl-xl ASON (FA) were intravenously administered to rabbits and mice. The blood samples from rabbits and organs from mice were collected, respectively. The radioactivity of the blood and tissues samples were measured.
Results: The clearance of the four kinds of liposomes and FA exhibited bicompartmental behaviors. Compared with others, NA demonstrated favourable pharmacokinetic properties characterized with enhancement of T9(1/2 alpha) and T(1/2 beta), increased area under concentration-time curve, and decreased liver uptake. Higher uptake in the liver, spleen and kidney of mice and lower uptake in the brain, muscle, and bone of mice were observed shortly after intravenous injection of the four different kinds of liposomes and FA. A 30% decrease in uptake of NA was found in the liver of mice four hours after intravenous injection compared with the uptake of CA. No significant differences were found in the uptake of the four kinds of liposomes in the spleen of mice (P > 0.05).
Conclusion: NA is promising as a carrier for radio-antisense therapy.
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