脂质体作为淋巴导向给药系统的实验研究  

Experimental Study on Liposomal Drug Delivery System for Lymphatic Targeting

作　　者：俸灵林[1,2] 张磊[1,3] 闫志强[1] 顾炳[1] 王晨瑜[1] 陆伟跃[1] 

机构地区：[1]复旦大学药学院,上海201203 [2]上海市计划生育科学研究所国家人口和计划生育药具重点实验室,上海200032 [3]诺华(中国)生物医学研究有限公司,上海201203

出　　处：《生物物理学报》2010年第8期735-749,共15页Acta Biophysica Sinica

基　　金：国家自然科学基金(30672545);国家重大新药创制专项基金(2009ZX09310-006);国家重大科学研究计划基金(2010CB934000)项目~~

摘　　要：组织间隙注射脂质体给药是较为理想的淋巴导向给药方式,而淋巴系统的导向速度慢、效率低,是亟待解决的难题。本文通过自制多种功能性膜材料,制备了不同理化性质的脂质体;采用放射性示踪法研究脂质体在大鼠体内的组织分布,并对脂质体粒径、表面电荷及PEG修饰对淋巴导向性的影响进行了评价;建立了注射部位吸收、淋巴结和血液动力学模型,并进行小鼠体内药动学试验,研究脂质体从组织间隙经毛细淋巴管吸收的向心循环入血过程。结果表明,脂质体粒径越小（如50nm）、表面荷负电且PEG修饰,淋巴导向效率越高;局部残留越少,经淋巴回血量越多。结果提示：脂质体具有较好的淋巴导向性,优劣程度与其理化性质有关;组织间隙中＂液体静压力差＂是脂质体导向淋巴系统的动力。As to the treatment of lymphatic metastases which is one of the most challenging difficulties in clinical practice,interstitial injection of liposomal drug delivery system has been considered preferable.But there are some problems such as the inadequate lymphatic drainage and lower targeting efficiency.In this study,several functional membrane materials were firstly synthesized for preparing different liposomes with different characteristic.We investigated the distribution of radiolabeled liposome and influence of liposomal size,surface charge and PEG modification on lymph node uptake and local resident of liposome after s.c.injection in rats.Based on the physiological nature of interstitial and main pathways of liposome in lymphatic system,there kinetic model were established and pharmacokinetics for liposome absorbed from injection site,uptake by lymph nodes and returned into blood were evaluated.The results show particle size is the most important factor influencing the lymphatic uptake of liposomes.Smaller the liposomes are,the less local retention,the more lymphatic drainage and the more back to systemic circulation were achieved.Meanwhile,negative electricity and PEG modification could also enhance lymphatic targeting of liposomes.Furthermore,the hydrostatic pressure gradient might be the main ＂driver＂ to improve the lymphatic absorb after interstitial injection of liposomes.

关 键 词：脂质体 组织间隙注射 淋巴导向 液体静压力差 动力学 

分 类 号：R94[医药卫生—药剂学]