目的 制备一种具有缓释作用的柚皮素(NG)新型纳米结构脂质载体(NG-NLC),并对其理化性质进行初步考察.方法 以乳化蒸发-低温固化法制备NG-NLC.采用星点设计-效应面法考察柚皮素-脂质材料比、单硬脂酸甘油酯-辛癸酸甘油酯比,以及乳化剂用量对包封率和载药量的影响.通过包封率、载药量、粒径、DSC分析以及体外释放度来评价NG-NLC的特性.结果 经过处方优化,确定NG-NLC最佳工艺条件为柚皮素-脂质材料比为20.77,单硬脂酸甘油酯-辛癸酸甘油酯比为1.85,乳化剂用量为58.45 mg,制备的NG-NLC包封率为(80.13±1.45)%,载药量为(3.59±0.06)%,平均粒径为(134.1±9.1)nm,多分散系数(PDI)为0.152±0.044;体外释放实验表明,NG-NLC在pH 7.4的缓冲溶液中前期有突释现象,后期则有缓释特征.结论 采用乳化蒸发-低温固化法成功制备了NG-NLC,为柚皮素的临床应用奠定了基础.

Objective To prepare novel naringenin-loaded nanostructured lipid carriers (NG-NLC) and investigate their physicochemical properties. Methods The NG-NLC were prepared by emulsion-evaporation-solidified at low temperature (EESLT) method. Central composite design-response surface methodology (CCD-RSM) was used to optimize the formulation of NG-NLC. Naringenin/lipid materials ratio, glycerol monostearate (GMS)/medium chain triglycerides (MCT) ratio, and emulsifier concentration were identified as key factors which were responsible for entrapment efficiency (EE) and drug loading (LD) of NG-NLC. The mean diameter, DSC analysis, and in vitro release characteristics of NG-NLC were investigated to evaluate their physicochemical properties. Results After the formulation optimization, the naringenin/lipid materials ratio was 20.77, GMS/MCT ratio was 1.85, and emulsifier concentration was 58.45 mg. The EE of NG-NLC was (80.13 ± 1.45)%, LD was (3.59 ± 0.06)%, average diameter of particles was (134.1 ± 9.1) nm, and polydispersity index (PDI) was 0.152 ± 0.044. In vitro release test revealed that the drug could be sustained-released from NG-NLC in buffer solution (pH 7.4) after a burst release in initial phase. Conclusion The EESLT method could be employed to prepare NG-NLC, which may lay the foundation for its further clinical application.

重庆市自然科学基金项目(cstc2012jjA10021);高等学校博士学科点专项科研基金(20125503120003);重庆市卫生局医学科研项目(2013-2-060);重庆医科大学大学生科学研究与创新实验项目(201432,201244,201217);重庆市教育委员会科学技术研究项目(KJ120307);海扶之星学生科研基金项目(XS201309)