Multivesicular liposomes. Sustained release of the antimetabolite cytarabine in the eye.

We entrapped the antimetabolite cytarabine hydrochloride in a multivesicular liposome for sustained drug delivery to the eye. The in vitro half-life of cytarabine release from these liposomes was 359 hours. Following subconjunctival administration of 6 mg of cytarabine to 12 rabbits, the tissue half-life of drug at the injection site was 52.5 hours in the six rabbits treated with liposomes compared with 0.2 hours in the six nonliposome controls treated with the same amount of drug in normal saline solution. The aqueous humor drug concentration peaked after 1.5 hours in both the experimental (0.4 mg/L) and control (19 mg/L) groups. In control eyes, the cytarabine level of both the tissue and aqueous humor had decreased to less than 1% of peak value by eight hours. In the liposome-treated eyes, almost 30% of the cytarabine remained in the conjunctiva and episcleral tissue after 72 hours. The difference in cytarabine levels in tissue between the liposome-treated group and controls was highly significant. By controlling the rate of drug release, it may be possible to reduce the ocular toxicity and increase the efficacy of this drug for treating ocular proliferative disorders.