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Multivesicular Liposomes Containing 1-ß-D-Arabinofuranosylcytosine for Slow-Release Intrathecal Therapy¹

Division of Hematology/Oncology, Department of Medicine, Cancer Center T-012A [S. K., D. J. K., S. B. H.], and Department of Psychiatry [M. A. G.], University of California, San Diego, La Jolla, California 92093

Optimal anticancer treatment with cell cycle-specific antimetabolites requires maintenance of a cytotoxic drug level for a prolonged period of time. We explored the use of multivesicular liposomes as a slow-release depot of 1-ß-D-arabinofuranosylcytosine for intrathecal administration. The intrathecal half-life of the liposome-encapsulated drug was 148 h, in contrast to the half-life of 2.7 h for the unencapsulated free drug, in a Sprague-Dawley rat model. The prolonged maintenance of a therapeutic drug level may increase efficacy, and the elimination of the very high peak level may decrease toxicity.

¹ This study was supported in part by USPHS Grants CA-01082, CA-35309, and CA-23100 from the National Cancer Institute, NIH, Department of Health and Human Services. This work was conducted in part by the Clayton Foundation for Research, California Division.

² To whom requests for reprints should be addressed, at Dept. of Medicine, T-012A, University of California, San Diego, La Jolla, CA 92093.

³ Supported by a Research Scientist Development Award from the National Institute of Mental Health (MH-00188).

⁴ Clayton Foundation Investigator.

Received 11/17/86. Revised 4/24/87. Accepted 4/29/87.

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