Yamamura K, Iwata H, Osada T, Yano K, Yotsuyanagi T, Nabeshima T
Department of Hospital Pharmacy, Nagoya University of School of Medicine, Japan.
J Biomed Mater Res. 1995 Oct;29(10):1249-53. doi: 10.1002/jbm.820291012.
This study was conducted to investigate whether hydroxyapatite (HAP) is appropriate as a percutaneous drug carrier for estradiol (E2) for the suppression of bone loss. Ten-week-old female Sprague-Dawley rats were subjected either to bilateral ovariectomy (OVX) or to sham surgery (control). Ovariectomized rats were implanted percutaneously with E2-HAP disks containing low, medium or high doses of estradiol (50, 250, or 500 micrograms E2/rat, respectively). Ovariectomized rats without implant and OVX rats implanted only with HAP served as additional controls. All rats were sacrificed 90 days after surgery. At the end of the experiment, bone mineral density of the lumbar spine was measured by dual energy X-ray absorption, and serum E2 was assayed by radioimmunoassay. The bone mineral density of OVX and HAP-treated OVX rats decreased by 18% compared to sham surgery rats, but decreased by only 13, 7, and 3% in rats treated with 50, 250, and 500 micrograms E2/rat, respectively. The in vitro release of E2 from E2-HAP devices was determined by an HPLC method. Estradiol release from the HAP devices followed almost a zero-order kinetics. Estradiol remained intact in E2-HAP implants for up to six months when stored at 5, 25, and 40 degrees C. This study indicates that E2-HAP implants are effective in suppressing bone loss in the spine of OVX rats in a dose-dependent manner.
本研究旨在探讨羟基磷灰石（HAP）作为雌二醇（E2）的经皮给药载体用于抑制骨质流失是否合适。将10周龄的雌性Sprague-Dawley大鼠进行双侧卵巢切除术（OVX）或假手术（对照）。对去卵巢大鼠经皮植入含有低、中、高剂量雌二醇（分别为50、250或500微克E2/只大鼠）的E2-HAP圆盘。未植入的去卵巢大鼠和仅植入HAP的OVX大鼠作为额外对照。所有大鼠在手术后90天处死。实验结束时，通过双能X线吸收法测量腰椎骨密度，并用放射免疫分析法测定血清E2。与假手术大鼠相比，OVX大鼠和HAP处理的OVX大鼠的骨密度降低了18%，但在分别用50、250和500微克E2/只大鼠处理的大鼠中，骨密度仅分别降低了13%、7%和3%。通过高效液相色谱法测定E2从E2-HAP装置中的体外释放。E2从HAP装置中的释放几乎遵循零级动力学。当在5、25和40℃储存时，E2在E2-HAP植入物中可保持完整长达6个月。本研究表明，E2-HAP植入物能以剂量依赖的方式有效抑制OVX大鼠脊柱的骨质流失。
