Hydroxyapatite ceramics for continuous delivery of heparin.

The goal of this investigation is to develop a ceramic system for delivering therapeutic amounts of heparin continuously from subcutaneous implants. Hydroxyapatite (HA) ceramic reservoirs were used for the continuous delivery of heparin in both in vitro and in vivo environments. Each reservoir was loaded with heparin. The open end was then sealed with a silastic medical adhesive and sterilized by ethylene oxide. A total of 15 capsules were used for conducting the in vitro experiments. Each capsule (control, sham, 1400, 2800, 4200 units heparin) was suspended in a vial containing 100 ml phosphate buffered saline (pH 7.4) at 37 degrees C. A one ml aliquot was withdrawn from each serum bottle at fixed intervals for three weeks, and assayed for heparin by the Sigma Heparin Clotting Assay. The largest amount of heparin was released from the capsule containing 4200 units of heparin and the smallest amount was released from the capsule containing 1400 units of heparin. Thirty Holtzman rats (140 +/- 15 g.) were used in the in vivo experiment. The rats were equally distributed into five groups (control, sham, 1400, 2800, and 4200 units of heparin). Animals in four of the five groups were implanted with HA capsules containing various amounts of heparin. Capillary tube clotting times were observed at regular intervals. Six days following implantation, the clotting times of the blood obtained from rats implanted with heparin-containing capsules was significantly higher (6.3 +/- 0.07 minutes) than the clotting times of blood obtained from shams and controls (4.3 +/- 0.03 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)