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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。
The interstitial injection of liposomes is an ideal lymphatic delivery method, while the lymphatic system is slow and inefficient, which is an urgent problem to be solved. In this paper, a variety of self-made functional membrane materials, preparation of different physical and chemical properties of liposomes; using radioactive tracer liposomes in vivo tissue distribution, and liposome size, surface charge and PEG modification The effects of lymphatic guiding were evaluated. Absorption, lymph node and hemodynamic models at the injection site were established. The pharmacokinetics test in mice was carried out to study the centripetal reorganization of the liposomes absorbed from the interstitial space through the lymphatic capillaries Blood process. The results showed that the smaller the liposome size (eg, 50 nm), the lower the surface charge and the more PEG-modified, the higher the lymphatic targeting efficiency. The results suggest that the liposomes have good lymphatic orientation, and the degree of the liposomes is related to their physico-chemical properties. The interstitial “hydrostatic pressure difference” is the motility of the liposome-directed lymphatic system.