Sustained delivery of 3H-thymidine by means of ceramic capsules in rats

The use of both oral and intravenous administration of 3-azido-2,3-dideoxythymidine (AZT) to treat AIDS patients is associated with negative side effects, including toxic effects on bone marrow. This study was designed to investigate the release of deoxynucleoside thymidine, the normal counterpart of AZT, by means of ALCAP ceramic implantable capsules in rats. ALCAP capsules (1.79 +/- 0.03 g/cm3) were impregnated with a solution of polylactic acid (2% wt/vol) in chloroform. Each capsule was loaded with 40 mg of unlabeled thymidine and 10 microCi of 3H-thymidine. A total of 60 SD-male rats were distributed into three groups (sham, control, and experimental). Each experimental rat was implanted intraperitoneally with a thymidine loaded ceramic capsule. Blood samples were collected at weekly intervals from each rat, for eight weeks, via the tail artery. A total of 351 +/- 9.12, 308 +/- 11.29, 350 +/- 21.28 and 322 +/- 31.76 micrograms/ml of thymidine was released from the ceramic capsule at the end of 14, 28, 42, 56, days, respectively. The data obtained shows that ALCAP ceramic capsules can deliver thymidine in a controlled, safe, and sustained manner in rats for a minimum duration of 120 days. It also suggests that ALCAP capsules probably can be used to deliver nucleosides, such as AZT, in a sustained manner for long durations in mammalian systems, including humans.