STEALTH ME.PEG-PLA NANOPARTICLES AVOID UPTAKE BY THE MONONUCLEAR PHAGOCYTES SYSTEM

STEALTH ME.PEG-PLA NANOPARTICLES AVOID UPTAKE BY THE MONONUCLEAR PHAGOCYTES SYSTEM
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DOI:
10.1002/jps.2600840420
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发表时间:
1995-04-01
影响因子:
3.8
通讯作者:
VEILLARD, M
VEILLARD, M
中科院分区:
医学3区
文献类型:
--
作者:
BAZILE, D;PRUDHOMME, C;VEILLARD, M

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采用沉淀-溶剂扩散法,以聚乙二醇-聚乳酸(Me.PEG-PLA)嵌段共聚物及其与聚乳酸(PLA)的共混物为原料,制备了纳米粒子。通过在制剂中引入[C-14]PLA标记的这些纳米颗粒显示出比F68包被的PLA纳米颗粒更慢地被培养的THP-1单核细胞以PEG链长度依赖性方式捕获。在体内,静脉内给予大鼠的Me.PEG-PLA纳米颗粒在血浆中的半衰期与F68包被的PLA纳米颗粒相比增加了180倍。这种单核吞噬细胞系统的避免解释根据构象模型,其中在颗粒表面的PEG密度是一个关键参数。
Nanoparticles were prepared from methoxy poly(ethylene glycol)poly(d,l-lactic acid) block copolymers (Me.PEG-PLA) or blends of Me.PEG-PLA and PLA by the precipitation-soivent diffusion method. These nanoparticles, labeled by introducing [C-14]PLA in the formulation, were shown to be more slowly captured by cultured THP-1 monocytes than F68-coated PLA nanoparticles, in a PEG chain-length-dependent manner. In vivo, the half-life in plasma of the Me.PEG-PLA nanoparticles that were intravenously administered to rats is increased by a factor 180 compared with the F68-coated PLA nanoparticles. This mononuclear phagocytes system avoidance was explained according to a conformation model in which the PEG density at the surface of the particles is a key parameter.