课题背景：课题由2007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。国内外已上市的有鬼臼毒素酊剂、软膏和凝胶，本课题致力于鬼臼毒素固体脂质纳米粒的系列研究，具有重要的实际应用价值。

应用要点：①用毒性低、生物相容性好的固体脂质材料为载体，将药物吸附或包裹于其中，制备鬼臼毒素固体脂质纳米粒，是临床研究的新剂型。②合理的冻干条件增加了冻干工艺的科学性，恰当的冻干保护剂提高了冻干粉剂型的质量。③使用超速离心法结合高效液相检测包封率，增加了高科技含量。

同行评价：实验选用海藻糖、甘露醇为冻干保护剂，探索一种制备鬼臼毒素固体脂质纳米粒冻干粉的方法，并对其理化性质进行了考察。选题具有一定实际应用意义，实验设计合理，方法正确，其结果为下一步临床研究提供了可靠的参考数据。

摘要
目的：制备含有不同冻干保护剂的鬼臼毒素固体脂质纳米粒(POD-SLN)冻干粉，并考察其理化性质，筛选出最佳配方。
方法：实验于2006-12/2007-11在南方医科大学药学部实验室完成。冻干配方为15%海藻糖、15％甘露醇和二者联用各取 5％，冷冻干燥制作冻干粉制剂。扫描电镜下观察冻干粉复溶后粒子形态，Image -Pro Plus 6.0软件计算粒径大小，高效液相考察固体脂质纳米粒的药物包封率，并考察冻干粉的外观、复溶和4 ℃保存对其影响，评价不同辅料对冻干品的影响。
结果：①外观和复溶情况：海藻糖冻干粉、海藻糖联用甘露醇冻干粉表面均松脆多孔，疏松，复溶较快，约需20 s，甘露醇冻干粉表面较光滑，结构致密，饼状，复溶较慢，需借助外力。冻干粉样品4 ℃冰箱放置24 h、1，3，6个月其外观和复溶均无明显变化。②电镜下粒子形态：呈圆形或椭圆形，分布较均匀，冻干前后无明显差异。③粒径：未加冻干保护剂时为（82.65± 18.43）nm，加入海藻糖、海藻糖联用甘露醇、甘露醇后分别为（94.78±21.94），（109.26±16.15），（114.63±21.42）nm。④包封率：未加冻干保护剂时为 87.4%，加入海藻糖、海藻糖联用甘露醇、甘露醇后分别为86.2%，80.3%，79.6%。
结论：以15%海藻糖为冻干保护剂制备的鬼臼毒素固体脂质纳米粒冻干粉粒径较小，包封率高，稳定性好，其制备工艺合理可行。
关键词: 鬼臼毒素；固体脂质纳米粒；冻干；海藻糖；生物材料；药物载体材料

谷东风，曾抗，李国锋，史毓杰，江中洪，杨莉.鬼臼毒素固体脂质纳米粒冻干粉的制备及理化性质考察[J].中国组织工程研究与临床康复，2008，12(10):1835-1838 [www.zglckf.com/zglckf/ejournal/upfiles/08-10/10k-1835(ps).pdf]

Preparation and physicochemical characteristics of podophyllotoxin loaded solid lipid nanoparticles

Abstract

AIM：To prepare podophyllotoxin-loaded solid lipid nanoparticles (POD-SLN) powder containing different cryoprotectors, and study its physicochemical characteristics for searching the optimal prescription.
METHODS: The experiment was carried out in the laboratory, Department of Pharmacy, Nanfang Hospital of Southern Medical University from December 2006 to November 2007. Cryopreservation prescription consisted of 15% trehalose, 15% Mannitol and combination of the two ones (each 5%) as cryoprotectors to prepare POD-SLN powder. Transmission electron microscope, Image-Pro Plus 6.0 software, and high-performance of liquid chromatography were used to detect the particle diameter and entrapment efficiency, respectively. Powder appearance and dissolution, as well as the stability when stored at 4 ℃ were all investigated to evaluate the effect of different adjuvant on the powder.
RESULTS: ①Appearance and dissolution: The surface of POD-SLN powder contained 15% Trehalose or combination of 5% Trehalose and 5% Mannitol looked slake and porous, and the two kinds of POD-SLN powder dissolved in water rapidly, about 20 seconds. The surface of POD-SLN powder contained 15% Mannitol was smooth, dense, cake-shaped, and hard to dissolve. Ultrasonic oscillation could be conducted with assistance of external force. When stored at 4 ℃ for 24 hours, 1 month, 3 months and 6 months, the powder samples showed no significant differences of appearance and dissolution.②The particles of POD-SLN powder was round or ellipse, with even distributions. There was no significant difference before and after cryopreservation.③The particle diameter of POD-SLN powder without cryoprotectors and with Trehalose, Mannitol or combination of the two were (82.65±18.43) nm, (94.78±21.94) nm, (114.63±21.42) nm, (109.26±16.15) nm separately.④The entrapment efficiency of POD-SLN powder with cryoprotectors and with Trehalose, Mannitol or combination of the two were 87.4%, 86.2%, 79.6%, 80.3% separately.
CONCLUSION: The small particle diameter, high entrapment efficiency and good stability of POD-SLN powder contained 15% Trehalose are satisfying, and the preparation process is practical.

Gu DF, Zeng K, Li GF, Shi YJ, Jiang ZH, Yang L.Preparation and physicochemical characteristics of podophyllotoxin loaded solid lipid nanoparticles.Zhongguo Zuzhi Gongcheng Yanjiu yu Linchuang Kangfu 2008;12(10):1835-1838(China)
[www.zglckf.com/zglckf/ejournal/upfiles/08-10/10k-1835 (ps).pdf]