In vivo delivery of estradiol from ceramic drug delivery devices

Ceramic drug delivery systems (CDS) are capable of delivering a wide variety of chemicals and/or biologicals directly into the systemic circulation in a continuous manner over long intervals with minimum risk to the recipient. The objectives of the present study were: (i) to determine the capability of tricalcium phosphate (TCP) capsules to deliver estradiol (E) in a sustained manner into the circulation of intact adult male rats, and (ii) to investigate the physiological responses associated with the presence of constant levels of estradiol in adult male rats. Microcrystals, particle size of less than 38 um, of TCP powder were prepared using standard procedures. TCP capsules with an outer diameter of 0.8 cm and an inner diameter of 0.4 cm were prepared by compressing calcined materials in a cylindrical dye at a compression load of 700 Kg. The ceramic capsules had a final density of 1.82 +/- 0.03 gm/cm3. A total of 54 adult male rats were divided into three groups of 18. Each rat in group I was implanted intraperitoneally with 2 CDS, one TCP capsule impregnated with polylactic acid (PLA) and the second nonimpregnated TCP capsule. Each capsule contained 40 mg of E. Animals in group II were implanted with two similar capsules without E (shams) and group III animals which served as intact controls were not fitted with CDS. Eight rats from each group were euthanized 2, 4, or 6 months following CDS implantation. Ceramic capsules were retrieved from the euthanized animals and the amount of E left within the ceramic was determined.(ABSTRACT TRUNCATED AT 250 WORDS)