右旋去氧娃儿藤宁纳米结构脂质载体的制备和包封率测定

Preparation and Determination of Entrapment Efficiency of S-( +)-Deoxytylophorinidine Nanostructured Lipid Carriers

目的:制备右旋去氧娃儿藤宁(CAT)纳米结构脂质载体(CAT-NLC),并建立CAT-NLC包封率测定方法。方法:以油酸增溶CAT并与山俞酸甘油酯为复合脂质载体材料,采用热熔超声分散法制备CAT-NLC;以超滤离心法和葡聚糖凝胶柱法分离游离药物和载药纳米粒,采用HPLC法测定CAT-NLC包封率。结果:制备得到的CAT-NLC为规则球形或类球形,平均粒径为(146.0±1.8) nm,多分散系数为(0.270±0.000 9),Zeta电位为(-29.0±0.67) m V;透析法体外释放考察显示4 h内CAT的累积释放度为(53.3±3.8)%;超滤离心法和葡聚糖凝胶柱法均能有效分离游离药物和载药纳米粒,平均回收率分别为101.03%(RSD=1.53%,n=9)和100.3%(RSD=2.4%,n=9),采用更适合的葡聚糖凝胶柱法测定CAT-NLC包封率,结果为(80.70±1.80)%。结论:热熔超声分散法制备得到的CAT-NLC,具有体外缓释特性,包封率较高;葡聚糖凝胶柱法可准确、可靠地测定CATNLC包封率。

Objective:To prepare S-(+)-deoxytylophorinidine(CAT)nanostructured lipid carriers(CAT-NLC)and establish a method to determine its entrapment efficiency.Methods:CAT-NLC was prepared by a melt-homogenization and ultrasonization technique by solubilizing CAT with oleic acid and using glyceryl behenate as the composite lipid carrier material.The free drug and drugloaded nanoparticles were separated by ultrafiltration centrifugation and Sephadex gel column,and CAT-NLC encapsulation efficiency was determinated by HPLC.Results:The prepared CAT-NLC was a regular spherical or spheroidal shape,the average particle diameter was(146.0±1.8)nm,the polydispersity coefficient was(0.270±0.0009),and the zeta potential was(-29.0±0.67)m V.The release in vitro by dialysis showed that the cumulative release rate of CAT-NLC was(53.3±3.87)%within 4 hours.Both ultrafiltration and dextran gel could effectively separate free drug and drug-loaded nanoparticles.The average recoveries were 101.03%(RSD=1.53%,n=9)and 100.3%(RSD=2.4%,n=9).The encapsulation efficiency of CAT-NLC was determined by a more suitable Sephadex gel column method,and the result was(80.70±1.80)%.Conclusion:The CAT-NLC prepared by the melt-homogenization and ultrasonization technique has the characteristics of sustained release in vitro and high encapsulation efficiency.The Sephadex gel column method can accurately and reliably determine the encapsulation efficiency of CAT-NLC.