BODY DISTRIBUTION OF FULLY BIODEGRADABLE [C-14] POLY(LACTIC ACID) NANOPARTICLES COATED WITH ALBUMIN AFTER PARENTERAL ADMINISTRATION TO RATS
BODY DISTRIBUTION OF FULLY BIODEGRADABLE [C-14] POLY(LACTIC ACID) NANOPARTICLES COATED WITH ALBUMIN AFTER PARENTERAL ADMINISTRATION TO RATS
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DOI：
10.1016/0142-9612(92)90142-b
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发表时间：
1992-01-01
期刊：
影响因子：
14
通讯作者：
SPENLEHAUER, G
中科院分区：
文献类型：
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作者：
BAZILE, DV;ROPERT, C;SPENLEHAUER, G
以蛋白质为表面活性剂，通过高压乳化和溶剂蒸发制备了包覆人血清白蛋白（HSA）的完全可生物降解的聚乳酸（PLA）纳米颗粒（90-250 nm）。基于米氏定律和尺寸排阻色谱法，开发了一种新的分析工具，以确定溶剂蒸发后，蛋白质会饱和纳米粒子的表面，从而掩盖 PLA 核心。根据该技术，聚合物基质中没有封装HSA。合成了放射性标记的 [C-14]-PLA50，以追踪这种新药物载体在静脉注射后的命运。对大鼠给药。从血浆中清除白蛋白包被的纳米颗粒所需的时间明显长于未包被的纳米颗粒，但没有足够长的时间来靶向除单核吞噬细胞之外的细胞。从全身放射自显影和定量分布实验推断，C-14标记的聚合物被肝脏、骨髓、淋巴结、脾脏和腹膜巨噬细胞快速捕获。 C-14 排泄后纳米颗粒降解问题得到解决。第一天 C-14 的消除很快（给药剂量的 30%），但随后减慢。事实上，如果 PLA 的代谢进行到乳酸，乳酸通过克雷布斯循环迅速转化为 CO2（总排泄量的 80% 由肺部完成），那么乳酸的合成代谢也可能发生，通过将 C-14 掺入内源性化合物中，导致持久的放射性残留物。
Fully biodegradable polylactic acid (PLA) nanoparticles (90-250 nm) coated with human serum albumin (HSA) were prepared by high-pressure emulsification and solvent evaporation, using the protein as surfactant. A new analytical tool was developed, based on Mie's law and size exclusion chromatography, to establish that, after evaporation of the solvent, the protein saturates the surface of the nanoparticles, masking the PLA core. According to this technique, no HSA is encapsulated in the polymer matrix. A radiolabelled [C-14]-PLA50 was synthesized to follow the fate of this new drug carrier after i.v. administration to rats. The time necessary to clear the albumin-coated nanoparticles from the plasma was significantly longer than for the uncoated ones but not extended enough to target cells other than mononuclear phagocytes. As deduced from whole-body autoradiography and quantitative distribution experiments, the C-14-labelled polymer is rapidly captured by liver, bone marrow, lymph nodes, spleen and peritoneal macrophages. Nanoparticle degradation was addressed following C-14 excretion. The elimination of the C-14 was quick on the first day (30% of the administered dose) but then slowed down. In fact, if the metabolism of the PLA proceeds to lactic acid which is rapidly converted into CO2 via the Krebs cycle (80% of the total excretion was fulfilled by the lungs), anabolism from the lactic acid may also have taken place leading to long-lasting radioactive remnants, by incorporation of C-14 into endogenous compounds.