盐酸表阿霉素纳米靶向制剂的缓释效应***★◆

摘要

背景：盐酸表阿霉素是一种广谱抗生素，目前临床使用的不足多为药物释放快、目标组织药物浓度低，静脉给药后广泛分布于体内各种组织器官，不良反应明显。目的：针对盐酸表阿霉素临床应用的不足，制备盐酸表阿霉素纳米靶向注射制剂。方法：以叶酸偶联牛血清白蛋白为载体，采用乳化-高压匀质法，制备盐酸表阿霉素纳米靶向注射制剂，以激光粒度分析仪测定纳米颗粒的粒径大小、粒径分布及 Zeta 电位，扫描电镜观察纳米颗粒的表面形态，高效液相色谱法分析白蛋白负载盐酸表阿霉素纳米制剂的包封率、载药量和释药性能。结果与结论：制备的盐酸表阿霉素纳米粒外观呈均匀球型，粒径分布较窄，平均粒径为(157.73±0.40) nm，平均 Zeta 电位为(-30.85±0.43) mV，载药量22.78%，包封率可达96.24%。体外模拟释药结果表明药物释放曲线分为两个阶段，突释阶段微球释药量在24 h内达42.6%，缓释阶段纳米粒释药持续时间长，在112 h 时释药量达84.1%，载药纳米粒的药物释放速率持续稳定。结果表明乳化结合高压匀质法制备的盐酸表阿霉素纳米靶向制剂粒径均匀，粒径范围分布窄，载药量和包封率高，具有一定的缓释作用。%BACKGROUND: Epirubicin hydrochloride is a kind of broad-spectrum antibiotics, and the disadvantages in the clinical application are faster drug release and low drug concentrations of target tissue. Epirubicin hydrochloride can widely distribute in various organs after intravenous administration with obvious side effects. OBJECTIVE: To prepare the epirubicin hydrochloride nano-targeted delivery according to the shortages of epirubicin hydrochloride in the clinical application. METHODS: The epirubicin hydrochloride nano-targeted delivery was prepared with the carrier of folate-conjugated epirubicin hydrochloride albumin nanoparticles by the method of emulsification-high pressure homogenization. Particles size, distribution and Zeta potential were detected by laser particle size analyzer. The morphology of epirubicin hydrochloride nanoparticles was observed by scanning electron microscope.In addition, encapsulation capability, loading content and drug release of the folate-conjugated epirubicin hydrochloride albumin nanoparticles were analyzed by high-performance liquid chromatography. RESULTS AND CONCLUSION: The results showed that the nanoparticles were spherical and wel distributed. The mean particle size was (157.73±0.4) nm, and mean Zeta potential was (-30.85±0.43) mV. The encapsulation efficiency was 96.24% and the loading content was 22.78%. The results of simulate drug releasing results showed that the drug release curve could be divided into two phases, microspheres release in the burst release phase could reach 42.6% at 24 hours, nanoparticles release could be lasted for a long time in the sustained-release stage, and the drug release could reach to 84.1% at 112 hours. The drug release rate of the drug-loaded nanoparticles remained stable. The epirubicin hydrochloride nano-targeted delivery prepared with emulsification-high pressure homogenization has uniform particle size, narrow size distribution, high encapsulation efficiency and loading content, and has certain release effect.