诺氟沙星—固体脂质纳米粒的制备及体外释药特性研究

郭杰 乔瑾 闫明明 郑文君 许蕊 隋小宇

摘 要 目的：优化诺氟沙星-固体脂质纳米粒的制备工艺，并考察其体外释药特性。方法：采用紫外分光光度法测定诺氟沙星的含量；采用超声-高压均质法制备诺氟沙星-固体脂质纳米粒。以包封率和粒径为指标，采用评分法对制备工艺进行单因素试验，并采用Box-Behnken响应面法优化制备工艺；通过透射电镜法观察诺氟沙星-固体脂质纳米粒的形态；通过体外释放试验考察其释药特性。结果：诺氟沙星检测质量浓度线性范围为0.2～1.2 μg/mL（r=0.999 5）。最优制备工艺脂质材料为三硬脂酸甘油酯，表面活性剂为大豆卵磷脂 ∶ 泊洛沙姆188=1 ∶ 2（m/m），剪切速度为15 000 r/min，脂药比为7.67 ∶ 1（m/m），药物质量浓度为8.91 mg/mL，超声时间为4.80 min，超声温度为65 ℃，均质压力为120 MPa，冻干保护剂为10%海藻糖。所得诺氟沙星-固体脂质纳米粒形态近似于球形，大小均一，平均粒径为（168.0±4.8）nm，平均包封率为（86.8±5.1）%；1 h内有突释现象，8 h内的累积释放度为（75.7±8.1）%。结论：制得的诺氟沙星-固体脂质纳米粒形态良好，粒径适宜，具有较好的体外缓释性。

关键词 诺氟沙星；固体脂质纳米粒；响应面法；超声-高压均质法；体外释放试验；包封率；粒径

中图分类号 R944.2 文献标志码 A 文章编号 1001-0408（2018）22-3068-06

DOI 10.6039/j.issn.1001-0408.2018.22.10

ABSTRACT OBJECTIVE： To optimize the preparation technology of Norfloxacin solid lipid nanoparticles and investigate its drug release characteristics in vitro. METHODS： The content of norfloxacin was determined by UV spectrophotometry. Norfloxacin solid lipid nanoparticles were prepared by ultrasound-high pressure homogenization. Using encapsulation rate and particle size as indexes， single factor tests of preparation technology were conducted by using the scoring method， and the Box-Behnken response surface method was used for optimization. TEM was used to observe its morphology of Norfloxacin solid lipid nanoparticles. The release characteristics were investigated by release test in vitro. RESULTS： The linear range of norfloxacin were 0.2-1.2 μg/mL （r=0.999 5）. The optimal technology was glycerol tristearate as lipid material， fabaceous lecithin： poloxamer 188 （1 ∶ 2，m/m） as surfactant， shearing velocity of 15 000 r/min， lipid-drug ratio of 7.67 ∶ 1， drug concentration of 8.91 mg/mL， ultrasonic time of 4.80 min， ultrasonic temperature of 65 ℃， homogeneous pressure of 120 MPa， freeze-dried protective agents of 10% trehalose. Norfloxacin solid lipid nanoparticles were nearly spherical in shape and uniform in size with average particle size of （168.0±4.8） nm. Average encapsulation rate was （86.8±5.1）%； burst release appeared within 1 h， and accumulative release rate was （75.7±8.1）% within 8 h. CONCLUSIONS： The prepared Norfloxacin solid lipid nanoparticles have good shape， suitable particle size and good sustained-release characteristics in vitro.

KEYWORDS Norfloxacin； Solid lipid nanoparticles； Response surface methodology； Ultrasonic-high pressure homogenization； Release test in vitro； Encapsulation rate； Particle size

諾氟沙星（Norfloxacin）是第三代喹诺酮类抗菌药物，其抗菌谱广，抑菌作用强[1]，但该药存在脂溶性和水溶性均较差、生物膜穿透能力弱、生物利用度低、口服吸收不好且生物半衰期仅有3～4 h等缺点[2-3]。固体脂质纳米粒（Solid lipid nanoparticles，SLN）以类脂为载体，将药物镶嵌在脂质材料表面或包裹于脂质核中，形成粒径为10 nm～1 μm的纳米给药体系，具有生物相容性好、毒性低、缓释性好等优点[4-5]。……