替米考星肺靶向微球的研制

Development of tilmicosin gelatin microspheres for targeting lung

采用乳化-化学交联法制备了替米考星肺靶向微球,并采用高效液相色谱法,通过MCPKP药代动力学软件分析,验证了该替米考星明胶微球在兔体内的肺靶向性。结果显示,替米考星明胶微球性质稳定、分散良好,且带有正电荷,平均粒径为11.20μm,粒径5.0～25.0μm的微球占总数的95.65%;载药量为39.83%,包封率为70.47%;形态圆整;体外释药半衰期(T50)为5.99 h,约在35 min时有突释效应,随后缓慢释放。替米考星明胶微球对肺的靶向效率较心脏、肌肉、肝和肾分别提高了5.05、3.04、4.60、3.47倍;肺、心脏、肌肉、肝和肾的相对摄取率分别为8.48%、1.72%、2.79%、1.85%和2.44%;肺、心脏、肌肉、肝和肾的峰浓度比分别为2.19、0.41、0.64、0.75和0.84。表明用优化的制备工艺制得的替米考星明胶微球有良好的肺靶向性,同时可以减轻替米考星的心脏毒性。

The lung targeting gelatin microspheres of tilmicosin （TMS-GMS） were prepared by emulsion chemical cross-linking method. With High Performance Liquid Chromatography （HPLC）, the lung targeting of TMS-GMS was validated in rabbits by MCPKP software. TMS-GMS was 11.20μm in mean of diameter, and 5. 0-25. 0 μm TMS-GMS accounted for 95. 65% of the total amount. TMS-GMS had smooth appearance, good stabilization, fluidity and positive charge. The average of TMS-GMS drug loading rate and entrapment rate were 39.83% and 70.47 %, respectively. The half-life of the drug release （T50） was 5.99 h in vitro, with an initial burst effect at about minute 35 and slow-release stage. The rates of TMS-GMS increased 5.05, 3.04, 4.60 and 3.47 times for heart, muscle, liver and kidney, respectively. The relative intake rates of gelatin microspheres of TMS were 8. 48%, 1.72%, 2.79%, 1.85% and 2.44% for lung, heart, muscle, liver and kidney, respectively. The ratio of peak concentration（Ce） was 2.19 （lung）, 0.41 （heart）, 0.64 （muscle）, 0.75 （liver） and 0.84 （kidney）, respectively. In summary, the newly formulated TMS possessed good lung targeting by the optimal technology, meanwhile lessened tilmicosin cardiac toxicity.