Multivesicular liposomes. Sustained release of the antimetabolite cytarabine in the eye
K. K. Assil and R. N. Weinreb
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.
