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首页> 外文期刊>Acta biomaterialia >In vitro and in vivo characteristics of core-shell type nanogel particles: optimization of core cross-linking density and surface poly(ethylene glycol) density in PEGylated nanogels.
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In vitro and in vivo characteristics of core-shell type nanogel particles: optimization of core cross-linking density and surface poly(ethylene glycol) density in PEGylated nanogels.

机译：核-壳型纳米凝胶颗粒的体外和体内特征：聚乙二醇化纳米凝胶中核交联密度和表面聚（乙二醇）密度的优化。

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摘要

The biocompatibility and body distribution of PEGylated polyamine nanogels composed of chemically cross-linked poly(2-N,N-(diethylamino)ethyl methacrylate) (PEAMA) gel cores surrounded by poly(ethylene glycol) (PEG) chains were investigated to evaluate their feasibility as drug nanocarriers for systemic administration. PEGylated nanogels with different cross-linking densities (1, 2, and 5mol.%) were prepared to evaluate their biocompatibilities by in vitro cytotoxicity assay, hemolysis assay, and in vivo acute toxicity assay. The toxic effect of the PEGylated nanogels derived from polyamine gel cores was significantly reduced when the cross-linking density was increased, and those with a cross-linking density of 5mol.% showed a remarkably high median lethal dose (LD(50)) value >200mgkg(-1),despite the abundance of amino groups in the core. One hour after intravenous injection the PEGylated nanogels were found to have been eliminated from the systemic circulation, and less than 1% of the injected dose (ID) remained in the bloodstream. To improve the blood circulation time by increasing the surface PEG density of the PEGylated nanogels post-PEGylation of the PEGylated nanogels (via the Menschutkin reaction between tertiary amines of the PEAMA gel core and bromobenzyl-terminated short PEG) was carried out. A biodistribution study of these post-PEGylated nanogels revealed that the blood circulation time of the nanogels was definitely prolonged as the PEG content was increased. Therefore, the precise design of PEGylated nanogels with increased cross-linking densities in their polyamine gel cores and increased surface PEG densities seems promising for systemic applications.
机译：研究了被聚（乙二醇）（PEG）链包围的化学交联的聚（2-N，N-（二乙基氨基）甲基丙烯酸乙酯）（PEAMA）凝胶核组成的PEG化聚胺纳米凝胶的生物相容性和身体分布，以评估其作为用于系统给药的药物纳米载体的可行性。制备了具有不同交联密度（1、2和5mol。％）的PEG化纳米凝胶，以通过体外细胞毒性测定，溶血测定和体内急性毒性测定来评估其生物相容性。当增加交联密度时，源自多胺凝胶核的聚乙二醇化纳米凝胶的毒性显着降低，而那些交联密度为5mol。％的纳米凝胶的中值致死剂量（LD（50））值非常高> 200mgkg（-1），尽管核心中有大量的氨基。静脉注射一小时后，发现聚乙二醇化的纳米凝胶已从体循环中消除，并且少于1％的注射剂量（ID）保留在血液中。为了通过增加PEG化纳米凝胶的PEG化后的PEG化纳米凝胶的表面PEG密度来改善血液循环时间（通过PEAMA凝胶核的叔胺与溴苄基封端的短PEG之间的Menschutkin反应）进行。对这些后聚乙二醇化纳米凝胶的生物分布研究表明，随着PEG含量的增加，纳米凝胶的血液循环时间肯定会延长。因此，在聚胺凝胶核中具有增加的交联密度和增加的表面PEG密度的PEG化纳米凝胶的精确设计对于系统应用而言似乎是有希望的。

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