鬼臼毒素固体脂质纳米粒冻干粉的制备及理化性质考察

Preparation and physicochemical characteristics of podophyllotoxin loaded solid lipid nanoparticles

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-ProPlus6.0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20s,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24h、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。

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 carded 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, l 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 cryopreservafion.③The particle diameter of POD-SLN powder without cryoprotectors and with Trehalose, Mannitol or combination of the two were （82.65± 1.8.43） nm, （94.78±21.94） rim, （114.63 ±21.42） nm, （109.26±16.15） nm separately. ④ The 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.