高压均质法制备载有维甲酸的纳米结构脂质载体  

Preparation of Nanostructured Lipid Carriers Loaded with Retinoic Acid by the High Pressure Homogenization Method

作　　者：张晓佳[1] 夏强[1] 马全红[1,2] 段磊[1] 顾宁[1] 

机构地区：[1]东南大学分子与生物电子学教育部重点实验室纳米科学与技术研究中心 [2]东南大学化学化工系,江苏南京210096

出　　处：《过程工程学报》2005年第1期54-57,共4页The Chinese Journal of Process Engineering

基　　金：江苏省计划发展委员会资助项目(编号:7607038009);国家自然科学基金资助项目(编号:60371027)

摘　　要：采用高压均质法制备了载有维甲酸(RA)的纳米结构脂质载体(NanostructuredLipidCarriers,NLC),并用透射电镜(TEM)、粒度分析仪、z电位仪和高效液相色谱仪(HPLC)对其进行了表征.结果表明,随高压均质循环次数的增加,NLC的均粒径从120nm减小到10nm,同时单分散性变差;NLC的微观形貌呈球形,表明其未结晶具有较好的载药能力;NLC将维甲酸浓度从20mg/mL(溶解于硅油)提高到56.26mg/mL,并能提高其光稳定性;NLC体系的稳定性良好,z电位高达(-30.90.6)mV,于4℃以10000r/min冷冻离心120min或避光保存6个月后粒径分布仍然基本不变,且可冷冻干燥(-40℃,0.01Pa)后长期保存.The poor aqueous solubility and instability of retinoic acid (RA) have limited its clinical use. Solid lipid nanoparticles (SLN) have a potential limitation which is the drug expulsion. This study was undertaken to overcome the limitation by loading RA in nanostructured lipid carriers (NLC). RA-loaded NLC was prepared by high pressure homogenization and characterized by transmission electronic microscope (TEM), particle size analyzer, zeta potential analyzer and high-performance liquid chromatography (HPLC). The results were as follows: (1) When the homogenization cycle number varied from 1 to 12, the mean particle size decreased from 120 nm to 10 nm, while P.I. (polydispersity index) increased from 0.26 to 0.69. (2) The spherical shape observed by TEM indicated a better drug loading capacity over SLN. (3) The concentration of all-trans retinoic acid (ATRA) in NLC reached 56.26 mg/mL compared to 20 mg/mL dissolved in silicone oil and the photostability of ATRA was improved so that the effective concentration of RA could keep for a longer time. (4) As far as the stability of NLC was concerned, its z potential value was (-30.90.6) mV and it remained stable after 120 min centrifugation (4℃, 10000 r/min) or 6 month light-proof storage. Furthermore, freezing-drying (-40℃, 0.01 Pa), which increased its mean particle size and reduced its P.I., could also be used to increase the NLC stability. Taken together, RA-loaded NLC is a promising drug form for clinical use.

关 键 词：纳米结构脂质载体(NLC) 高压均质 维甲酸(RA) 

分 类 号：R9[医药卫生—药学] TQ46[化学工程—制药化工]