盐霉素纳米结构脂质载体的制备及处方优化

摘要

目的:制备盐霉素纳米结构脂质载体(Sal-NLCs)并优化处方.方法:采用熔融乳化-低温固化法制备Sal-NLCs.采用星点设计-响应面法,以粒径、Zeta电位、包封率、载药量为评价指标,优化处方中Sal用量、油相中固态脂质双硬脂酸甘油酯与液态脂质辛癸酸甘油酯的质量比、表面活性剂聚氧乙烯35蓖麻油(EL)与聚乙二醇-15-羟基硬脂酸酯(HS15)的质量比及聚氧乙烯(40)硬脂酸酯(P40)的用量.考察所制Sal-NLCs的外观形态、粒径、多分散指数(PDI)、Zeta电位、包封率、载药量和体外释药机制.结果:最优处方为Sal0. 86 mg、双硬脂酸甘油酯40. 70 mg、辛癸酸甘油酯11. 30 mg、EL44. 05 mg,HS157. 95 mg、P403. 8 mg;所制 Sal-NLCs呈类圆形、分布均匀,粒径为(81. 81±2. 60)nm、PDI为0. 183±0. 042、Zeta电位为(-24. 9±3. 4) mV、包封率为(94. 35±1. 50)％、载药量为(1. 47±0. 04)％(n=5),24h内累积释放度达到(99. 81±3. 90)％(n=3),释放行为符合Higuchi模型,其中粒径、 Zeta电位、包封率、载药量与模型预测值的相对误差均小于4％.结论:按优化处方成功制得具有缓释效果的Sal-NLCs,且质量达到预期标准.%OBJECTIVE: To prepare Salinomycin nanostructured lipid carriers (Sal-NLCs) and optimize its formulation. METHODS: Sal-NLCs was prepared by emulsion evaporation-low temperature solidification method. Using particle size, Zeta potential, encapsulation efficiency and drug loading as evaluation indexes, central composite design-response surface methodology was used to optimize the amount of Sal, the ratio of solid lipid glyceryl bisstearate to liquid lipid glyceryl octanoate in oil phase, ratio of surface active agent polyoxyethylene 35 castor oil (EL) to polyethylene glycol-15-hydroxy stearate (HS 15), the amount of polyoxyethylene (40) stearate (P40). The morphology, particle size, polydispersity index (PDI), Zeta potential, encapsulation efficiency, drug loading and in vitro release mechanism of Sal-NLCs were investigated. RESULTS: The optimal prescription was as follows as Sal 0. 86 mg, glyceryl bisstearate 40.70 mg, glyceryl octanoate 11.30 mg, EL 44.05 mg, HS15 7.95 mg, P40 3.8 mg. Prepared Sal-NLCs was round-like and dispersed evenly. The particle size, PDI, Zeta potential, encapsulation efficiency and drug loading of prepared Sal-NLCs were(81.81 ± 2.60) nm, 0.183 ± 0.042, (-24.9 ± 3.4) mV,(94.35 ± 1.50)％ and (1.47 ±0.04)％ (n=5), respectively.24 h accumulative release rate was (99.81 ± 3.90)％ (n=3).Drug release behavior was in line with Higuchi model, and relative error of particle size, Zeta-potential, encapsulation efficiency and drug loading to predicted value of model were all lower than 4％. CONCLUSIONS: Sal-NLCs with sustained-release effect is prepared successfully according to optimized formulation, and its quality meets the expected standard.