SURFACE ENGINEERED NANOSPHERES WITH ENHANCED DRAINAGE INTO LYMPHATICS AND UPTAKE BY MACROPHAGES OF THE REGIONAL LYMPH-NODES
SURFACE ENGINEERED NANOSPHERES WITH ENHANCED DRAINAGE INTO LYMPHATICS AND UPTAKE BY MACROPHAGES OF THE REGIONAL LYMPH-NODES
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DOI：
10.1016/0014-5793(94)00351-3
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发表时间：
1994-05-09
期刊：
影响因子：
3.5
通讯作者：
DAVIS, SS
中科院分区：
文献类型：
--
作者：
MOGHIMI, SM;HAWLEY, AE;DAVIS, SS
胶体科学中使用的空间稳定的概念被应用于仔细地操纵皮下给药的模型聚苯乙烯纳米球的引流和淋巴分布。合成聚氧乙烯(POE)/聚氧丙烯(POP)嵌段共聚物的聚氧乙烯(POE)和泊洛沙姆(Poloxamer)系列已被用于生产空间稳定的纳米球。我们发现嵌段共聚物的稳定POE链的长度与纳米球引流和大鼠足垫皮肤毛细淋巴管中组织淋巴界面的通道之间存在相关性；POE链越长，粒子引流越快。由5-15个环氧乙烷单元组成的POE链的嵌段共聚物调节的纳米球在淋巴管中有效地调理；这一过程显著增强了区域淋巴结巨噬细胞的隔离(高达给药剂量的40%)。如果泊洛沙姆和泊洛沙姆的稳定POE链的尺寸超过范德华力的范围，则不会发生调理作用，快速排出的工程车辆逃脱区域节点的巨噬细胞的清除，到达体循环并在血液中停留较长时间。这些观察表明，基于聚合物涂层颗粒的淋巴输送组合物将在临床和实验医学中的许多应用中具有优势。
The concept of steric stabilization as used in colloid science is applied to carefully manipulate the drainage and lymphatic distribution of subcutaneously administered model polystyrene nanospheres. A wide range of synthetic polyoxyethylene (POE)/polyoxypropylene (POP) block co-polymers of poloxamine and poloxamer series have been used to produce sterically stabilized nanospheres. We have found a correlation between the length of the stabilizing POE chains of the block co-polymers and nanosphere drainage and passageway across tissue lymph interface in dermal lymphatic capillaries in the rat footpads; the longer the POE chains, the faster the particle drainage. Nanospheres conditioned with block co-polymers of POE chains of 5-15 ethylene oxide units are effectively opsonized in lymphatics; a process which dramatically enhances sequestration (up to 40% of the administered dose) by macrophages of the regional lymph nodes. If the dimensions of the stabilizing POE chains of the poloxamines and poloxamers exceed the range of the Van der Waals force of attraction, opsonization fails to occur and rapidly drained engineered vehicles escape clearance by macrophages of the regional nodes, reach the systemic circulation and remain in the blood for prolonged periods. These observations suggest that a lymphatic delivery composition based on polymer-coated particles will be advantageous for many applications in clinical and experimental medicine.