Moghimi S M, Hawley A E, Christy N M, Gray T, Illum L, Davis S S
Department of Pharmaceutical Sciences, University of Nottingham, UK.
FEBS Lett. 1994 May 9;344(1):25-30. doi: 10.1016/0014-5793(94)00351-3.
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.
胶体科学中使用的空间稳定化概念被应用于精心操控皮下注射的模型聚苯乙烯纳米球的引流和淋巴分布。多种泊洛沙明和泊洛沙姆系列的合成聚氧乙烯（POE）/聚氧丙烯（POP）嵌段共聚物已被用于制备空间稳定化纳米球。我们发现，嵌段共聚物中稳定化POE链的长度与大鼠脚垫真皮淋巴管中纳米球的引流以及穿过组织淋巴界面的通道之间存在相关性；POE链越长，颗粒引流越快。用含有5 - 15个环氧乙烷单元的POE链的嵌段共聚物处理的纳米球在淋巴管中能有效被调理；这一过程显著增强了区域淋巴结巨噬细胞的捕获（高达给药剂量的40%）。如果泊洛沙明和泊洛沙姆中稳定化POE链的尺寸超过范德华引力范围，调理作用就不会发生，快速引流的工程载体就能逃避区域淋巴结巨噬细胞的清除，进入体循环并在血液中长时间留存。这些观察结果表明，基于聚合物包被颗粒的淋巴递送组合物在临床和实验医学的许多应用中将具有优势。
