课题背景：迄今为止脂质体鬼臼毒素新型制剂的基础和临床研究国内外较少报道。课题由2003年广东省科技计划项目基金资助，2004年获全军医疗成果二等奖，2005年获广州市科技进步一等奖和南方医科大学南方医院医疗成果一等奖，2006年获广东省科技进步二等奖。课题研究成果目前已达到国内外先进水平，并为临床的应用提供了重要的参考价值。

应用要点：①采用毒性低、生物相容性好的固体和液态脂质材料为载体，将药物吸附或包裹于其中，制备鬼臼毒素-纳米脂质载体。②采用改良的乳化蒸发-低温固化法制备鬼臼毒素-纳米脂质载体是简便易行的方法。③鬼臼毒素-纳米脂质载体在室温下保存具有较高的稳定性。

同行评价：实验针对目前固体脂质纳米粒存在的不足之处，如有限的载药能力、储存过程中药物泄漏现象、纳米脂质体分散液的高水分含量等，实验探索了一种脂质纳米粒的制备方法。该方法具有载药能力高、稳定性强、缓释控释效果好等优点。并在此基础上，选择对尖锐湿疣疗效确切的鬼臼毒素作为主药，以脂质纳米粒作为载药材料，采用乳化蒸发-低温固化法制备了鬼臼毒素-脂质纳米粒，考察了载体的各项性能指标。研究结果对脂质纳米粒的应用提供了基础实验数据。

摘要
目的: 纳米脂质载体是近年来继固体脂质纳米粒发展起来的第2代亚微粒载药系统，具有较高的载药量和物理稳定性。探讨鬼臼毒素-脂质纳米粒（podophyllotoxin-loaded nanostructured lipid carrier，PPT-NLC）的制备方法及理化性质。
方法：实验于2006-08/2007-10在南方医科大学药学部实验室完成。选择固体脂质硬脂酸、单硬脂酸甘油脂和液态脂质油酸，采用改良的乳化蒸发-低温固化法制备PPT-NLC，用同法制备不含油酸的PPT-固体脂质纳米粒(Solid lipid nanoparticles，SLN)纳米粒混悬液。用透射电镜、Zeta电位仪、高效液相色谱法、pH计考察PPT-NLC理化性质，并比较SLN与NLC的包封率和稳定性。
结果：透射电镜下PPT-NLC外形呈圆形或椭圆形，平均粒径为（88.2±8.4）nm，多分散指数为0.190±0.085，Zeta电位为（-33.2±3.1）mV，包封率为86.6%。PPT-SLN分别为（75.3±16.2）nm，0.300±0.072，（-25.2±3.4）mV，包封率为76.5%。
结论：PPT-NLC制备工艺简单，分布均匀，稳定性较SLN好，包封率高。
关键词：纳米脂质载体；鬼臼毒素；固体脂质纳米载体；尖锐湿疣；生物材料

江中洪，曾抗，李国锋，谷东风，任非，史毓杰.鬼臼毒素纳米脂质载体的制备及质量考察[J].中国组织工程研究与临床康复，2008，12(6):1039-1042 [www.zglckf.com/zglckf/ejournal/upfiles/08-6/6k-1039(ps).pdf]

Preparation and characterization of podophyllotoxin-loaded nanostructured lipid carriers

Abstract

AIM：Nanostructured lipid carriers (NLC) have been developed as the second generation nanoparticulate delivery system, and possess the advantages of higher drug loading and physical stability. This study is designed to investigate the preparation method and physicochemical properties of podophyllotoxin-loaded NLC (PPT-NLC).
METHODS: This experiment was carried out in the laboratory of Pharmacy Department, Nanfang Hospital, Southern Medical University between August 2006 and October 2007. PPT-NLC was prepared by the method of emulsion evaporation and solidification at a low temperature. Monostearin, stearic acid and oleic acid were all used as lipids. PPT-solid lipid nanoparticles (PPT-SLN) suspension without oleic acid was also prepared by means of the same method. The physicochemical properties of the PPT-NLC were investigated with transmission electronic microscope, Zeta potential analyzer, high-performance liquid chromatography and pH value, respectively. Then drug entrapment efficiency and physical stability were compared between NLC and SLN.
RESULTS: Under transmission electronic microscope, PPT-NLC appeared as round or ellipse shape. The mean particle size, polydispersity index, Zeta potential and entrapment efficiency of PPT- NLC in the nanoparticles were (88.2±8.4) nm, 0.190±0.085, (-33.2±3.1) mV and 86.6%, respectively. Likewise, these index of PPT-SLN were (75.3±16.2) nm, 0.300±0.072, (-25.2±3.4) mV and 76.5%, respectively.
CONCLUSION: The PPT-NLC has simple preparation, even distribution, good stability and high efficiency of encapsulation compared with SLN.

Jiang ZH, Zeng K, Li GF, Gu DF, Ren F, Shi YJ.Preparation and characterization of podophyllotoxin-loaded nanostructured lipid carriers.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(6):1039-1042(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-6/6k-1039(ps).pdf]