In vitro influence of apatite-granule-specific area on human growth hormone loading and release

Although calcium phosphate biomaterials often are used as drug delivery systems (DDS) at bone sites, the conditions affecting the loading of the therapeutic agent (TA) have not been well documented. A human growth hormone (hGH) adsorption method was used in this study to investigate the influence of the formulated apatite (AP)-specific area on loading and release. AP powders were formulated with a 200-500 microm granulometry and various specific areas. Two milligrams of hGH in solution were deposited for 24 h at 37 degrees C on 100 mg of AP with different specific areas. The amount of hGH loaded was determined by immunoradiometric assay (IRMA) and eluted stain bioassay (ESTA) using Nb2 lymphoma rat cells. Although loading was not greatly influenced by a specific area between 3 and 25 m2/g, dependency was noted for higher specific areas. Human GH release was measured by IRMA and ESTA over a 33-day period, with half-time release between 25 and 79 h. Comparison of IRMA and ESTA measurements for the hGH amounts loaded showed that hGH biologic activity was conserved. Results indicate that it is feasible to control the quantity of TA loading on AP by modifying specific areas for in vivo applications.