醋酸亮丙瑞林脂质体及壳聚糖包衣脂质体经肠道及Caco-2细胞转运机制  

Mechanisms of action of transportation of liposomes and chitosan-coated liposomes containing leuprolide across intestine and Caco-2 cell

作　　者：郭健新[1] 平其能[1] 董隽[1] 李正荣[2] 李朝军[2] 

机构地区：[1]中国药科大学药剂教研室,江苏南京210009 [2]南京师范大学分子医学重点实验室,江苏南京210097

出　　处：《药学学报》2005年第1期65-70,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金重点资助项目(39930200).

摘　　要：目的　考察醋酸亮丙瑞林脂质体及壳聚糖包衣脂质体经大鼠肠道及Caco -2细胞的转运机制。方法　应用翻转肠囊法和Caco- 2细胞模型考察游离醋酸亮丙瑞林、脂质体包封的醋酸亮丙瑞林以及壳聚糖包衣脂质体中醋酸亮丙瑞林的转运特征。在Caco -2细胞水平考察壳聚糖浓度、加入次序对脂质体中醋酸亮丙瑞林渗透的影响。结果　游离醋酸亮丙瑞林的转运符合被动扩散的性质。相同实验条件下,脂质体中药物渗透量低于游离药物。可能是由于脂质体包封醋酸亮丙瑞林,阻止了药物向肠囊和Caco- 2细胞转运。但是脂质体对酶降解醋酸亮丙瑞林具有保护作用。壳聚糖促进脂质体中亮丙瑞林的转运,壳聚糖的促渗作用在 0. 1% -0 .5%浓度范围无明显差异。壳聚糖包覆脂质体后的促渗作用弱于其单独使用的促渗作用。结论　壳聚糖包衣醋酸亮丙瑞林脂质体兼有保护和促渗作用,可能促进醋酸亮丙瑞林的口服吸收。Aim To investigate the mechanisms of action of transportation of liposomes and chitosan-coated liposomes containing leuprolide across rat intestine and Caco-2 cell. Methods Everted-gut technique and Caco-2 cell were used to study the transport properties of free leuprolide, liposomes and chitosan-coated liposomes containing leuprolide. Caco-2 cell was used to study the effect of chitosan concentration and the order of addition on the permeation of liposomes. Results The transport of leuprolide was passive diffusion. Probably because the entrapment by liposomes prevents the transport of leuprolide across the rat intestine and Caco-2 cell, the permeation amount of leuprolide from liposomes was lower than that of the free drug. However, liposomes protected the leuprolide from degradation. Chitosan promoted the transport of leuprolide from liposomes and there was no obvious difference in enhancement effect from the concentration of 0.1% to 0.5%. On the other hand, the incubation of chitosan with liposomes may weak the enhancement effect of chitosan. Conclusion Chitosan-coated liposomes showed both protection and enhancement effect, therefore, they may promote the oral absorption of leuprolide.

关 键 词：醋酸亮丙瑞林 脂质体 壳聚糖包衣脂质体 转运 翻转肠囊法 CACO-2细胞 

分 类 号：R943.5[医药卫生—药剂学]