Biodistribution and targeting potential of poly(ethylene glycol)-modified gelatin nanoparticles in subcutaneous murine tumor model
Biodistribution and targeting potential of poly(ethylene glycol)-modified gelatin nanoparticles in subcutaneous murine tumor model
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DOI：
10.1080/10611860400013451
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发表时间：
2004-10-01
影响因子：
4.5
通讯作者：
Amiji, M
中科院分区：
文献类型：
--
作者：
Kaul, G;Amiji, M
目的：为了开发一种安全有效的全身给药的可生物降解的纳米粒递送系统用于实体瘤，比较明胶和聚（乙二醇）（PEG）-改性在携带皮下刘易斯肺癌（LLC）的雌性C57 BL/6 J小鼠中检查（聚乙二醇化）明胶纳米颗粒。在静脉内（i. v.）在携带LLC的小鼠中通过尾静脉给药。在不同的时间间隔，处死小鼠并收获血液、肿瘤和主要器官用于分析对应于纳米颗粒定位的放射性。测定回收剂量百分比，并将其标准化为液体或组织样品的重量。非房室药代动力学分析进行，以确定长循环的属性和优先的肿瘤靶向潜力的聚乙二醇化明胶纳米粒子在vivo .Results：从血浆和各种器官收集的放射性，很明显，大多数聚乙二醇化的纳米粒子是存在于血池或采取了由肿瘤块和肝脏。例如，3小时后，聚乙二醇化明胶纳米颗粒在血池中的浓度几乎是对照明胶纳米颗粒的2倍。与明胶纳米颗粒相比，由于PEG链的空间排斥效应，PEG化明胶纳米颗粒在血池中保留更长的时间。此外，约4-5%的回收剂量的聚乙二醇化明胶纳米颗粒存在于肿瘤块中长达12小时。的血浆和肿瘤的半衰期，平均停留时间，和下的曲线的面积的聚乙二醇化明胶纳米粒子显着高于那些为gelatin nanoparticle.Conclusions：本研究的结果表明，聚乙二醇化明胶纳米粒子具有长循环性能，并可以优先分布在肿瘤块后，全身交付。
Purpose : In order to develop a safe and effective systemically-administered biodegradable nanoparticle delivery system for solid tumors, the comparative biodistribution profiles of gelatin and poly(ethylene-glycol)(PEG)-modified (PEGylated) gelatin nanoparticles was examined in subcutaneous Lewis lung carcinoma (LLC)-bearing female C57BL/6J mice.Methods : Type-B gelatin and PEGylated gelatin nanoparticles were radiolabeled (I-125) for the in vivo biodistribution studies after intravenous (i.v.) administration through the tail vein in LLC-bearing mice. At various time intervals, the mice were sacrificed and blood, tumor, and major organs harvested for analysis of radioactivity corresponding to the localization of the nanoparticles. Percent recovered dose was determined and normalized to the weight of the fluid or tissue sample. Non-compartmental pharmacokinetic analysis was performed to determine the long-circulating property and preferential tumor targeting potential of PEGylated gelatin nanoparticles in vivo .Results : From the radioactivity in plasma and various organs collected, it was evident that the majority of PEGylated nanoparticles were present either in the blood pool or taken up by the tumor mass and liver. For instance, after 3 h, the concentrations of PEGylated gelatin nanoparticles was almost 2-fold higher in the blood pool than the control gelatin nanoparticles. PEGylated gelatin nanoparticles remained in the blood pool for a longer period of time due to the steric repulsion effect of the PEG chains as compared to the gelatin nanoparticles. In addition, approximately 4-5% of the recovered dose of PEGylated gelatin nanoparticles was present in the tumor mass for up to 12 h. The plasma and the tumor half-lives, the mean residence time, and the area-under-the-curve of the PEGylated gelatin nanoparticles were significantly higher than those for the gelatin nanoparticles.Conclusions : The results of this study show that PEGylated gelatin nanoparticles do possess long circulating properties and can preferentially distribute in the tumor mass after systemic delivery.