载异烟肼、利福平纳米羟基磷灰石-硫酸钙人工骨体外降解及释药研究

Degradation and release of isoniazid and rifampicin nano hydroxyapatite-calcium sulfate artificial bone in vitro

目的:观察载异烟肼(isoniazid,INH)、利福平(rifampicin,RFP)纳米羟基磷灰石(n HA)-硫酸钙(CSH)人工骨体外降解情况并探讨其释药性能。方法:将制备好的人工骨置于37℃模拟体液中降解,分别于24h、72h及1、2、4、6、8、10、12周九个时相点取出,采用扫描电子显微镜观察人工骨表面降解程度,测量其质量变化,采用电子万能试验机测试每个时相点人工骨的抗压强度。将人工骨置于37℃PBS中释药,采用高效液相色谱法(HPLC)分别检测24h、72h及1、2、4、6、8、10、12周九个时相点时的INH、RFP的释放浓度,并计算出累计释药百分数,观察药物的缓释程度。结果:随着浸泡时间的延长,人工骨体积逐渐减小,颜色变白;扫描电镜观察人工骨表面晶体结构逐渐消失,孔隙减少,最终人工骨表面被无结构的降解物所覆盖;人工骨的质量及其抗压强度都随着人工骨的降解而逐渐减小,第8周时抗压强度仍接近松质骨的强度。人工骨释药过程中,INH于24h、72h及1、2、4、6、8周时相点时的累计释药百分数分别为:44.58%、71.06%、90.23%、95.98%、98.27%、99.72%、100.00%,10、12周时未检出。RFP于24h、72h及1、2、4、6、8、10、12周九个时相点时的累计释药百分数分别为:2.70%、16.82%、39.96%、61.71%、83.88%、96.38%、97.63%、98.00%、98.26%。结论:载异烟肼、利福平纳米羟基磷灰石-硫酸钙人工骨在体外稳定降解,并具有持续时间较长的有效缓释性能。

Objectives： To observe the degradation and drug release properties of isoniazid（INH） and rifampicin（RFP） nano hydroxyapatite（nHA）-calcium sulfate （CSH） artificial bone in vitro. Methods： The prepared artificial bone was degraded in simulated body fluid at 37 degrees centigrade and taken out at 24h, 72h, 1w, 2w, 4w, 6w, 8w, 10w, 12W, respectively. The degradation degree of artificial bone surface was observed by scanning electron microscope, and the quality changes were measured. The compressive strength of artificial bone at each time point was tested by electronic universal test machine. The artificial bone was placed at PBS at 37 degrees centigrade for release, the release concentration of INH and RFP at nine phase points of 24h, 72h, 1w, 2w, 4w, 6w, 8w, 10w and 12w were detected by high performance liquid chromatography （HPLC）. The cumulative drug release percentage was calculated, and the drug release rate was observed. Results： With the prolongation of soaking time, the volume of artificial bone gradually decreased and the color became white. And the crystal structure of the artificial bone surface disappeared gradually and the pores decreased, and the surface of artificial bone was covered by unstructured degradations by scanning electron microscope. The quality and compressive strength of artificial bone decreased with the degradation of artificial bone. The compressive strength at eighth weeks was still close to the strength of cancellous bone. During the process of artificial bone release, the cumulative release percentages of INH at 24h, 72h, 1w, 2w, 4w, 6w, 8w were 44.58%, 71.06%, 90.23%, 95.98%, 98.27%, 99.72%, 100%, respectively, which at 10w and 12w were not detected. The cumulative drug release percentages of RFP at 24h, 72h, 1w, 2w, 4w, 6w, 8w, 10w and 12w nine phases were 2.70%, 16.82%, 39.96%, 61.71%, 83.88%, 96.38%, 97.63%, 98.00%, 98.26%, respectively. Conclusions： Isoniazid and rifampicin nano hydroxyapatite-calcium sulfate artificial bone degrades steadily in vitro, and it has long and effective release performance.