全反式维甲酸纳米结构脂质载体的制备及稳定性研究  

Preparation and Stability of All-trans Retinoic Acid Loaded Nanostructured Lipid Carriers

作　　者：马全红[1,2] 郝晓帧[1] 周华锋[1,2] 童杉[1] 夏强[2] 顾宁[2] 

机构地区：[1]东南大学化学化工学院,南京210096 [2]东南大学生物电子学国家重点实验室,江苏省生物材料与器件高技术重点实验室,南京210096

出　　处：《中国药学杂志》2006年第16期1244-1249,共6页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(20573019;90406023;60371027);江苏省自然科学基金创新人才项目资助(BK2002404)

摘　　要：目的制备全反式维甲酸纳米结构脂质载体，考察其稳定性。方法以生理相容的单硬脂酸甘油酯、棕桐酸、硬脂酸或它们的混合物作为固体脂质基材，以大豆油作为液态脂质基材，采用高压均质法制备全反式维甲酸（ATRA）纳米结构脂质载体（NLC）（ATRA-NLC），并采用光子相关光谱（PCS）、Zeta电位仪、透射电镜（TEM）、高效液相色谱（HPLC）考察其理化性质。结果单硬脂酸甘油酯是较好的固体脂质基材．制备的NLC粒径在94．8～129．3nm之间；载药后NFRA—NLC粒径稍增大，大都呈完整的球形。NLC作为ATRA的药物载体，载药量提高到146．50mg·L^-1并能显著降低ATRA的光降解速率。ATRA-NLC体系的Zeta电位负于30mV，4℃保存22个月后粒径基本保持不变。结论ATRA包封在NLC中，明显提高ATRA载药量和化学稳定性，且物理稳定性好，可望成为防治增殖性玻璃体视网膜病变（PVR）的一种新型药物载体。OBJECTIVE To investigate that all-trans retinoic acid （ATRA） loaded in nanostructured lipid carriers （NLC） favorably improve the solubility and chemical stability of ATRA. METHODS ATRA-NLC were produced by high pressure homogenization of mixed biocompatible lipids, such as glyceryl monostearate, stearie acid, palmitic acid or their mixture and soybean oil. Their properties including size, Zeta potential, microcosmic mnrphology, loading capacity and stability were investigated by photon cnrrelation spectroscopy （PCS）, Zata potential analyzer, transmission electronic microscope （TEM） and high-peffnnnance liquid chromatography （HPLC） respectively. The optimization of preparatinn parameters of ATRA-NLC was performed. RESULTS Glyceryl monostearate with weak surface activity was a preferable solid lipid matrix. The average diameters of NI,C produced under optimal experimental conditions were between 94.8 nm and 129.3 nm. The average particle diameters of drug-loaded NLC were, larger than that of drag-free NLC. TEM result showed that ATRA-NLC were nearly spherical nanoparicles, Mixed lipid improved the loading capacity of ATRA. The degradation velocity of ATRA . was significantly slowed down when ATRA was loaded into the NLC. NLC was stable during the storage of 22 months at 4 ℃. CONCLUSION The loading capacity and chemical stability of ATRA are significantly improved by the incorporation in NLC. ATRA-NLC is a very potential dosage form to prevent proliferative vitreoretinopathy （PVR）.

关 键 词：全反式维甲酸 纳米结构脂质载体 稳定性 载药量 

分 类 号：R94[医药卫生—药剂学] TQ46[医药卫生—药学]