Fibrin nanoparticles as Possible vehicles for drug delivery
Fibrin nanoparticles as Possible vehicles for drug delivery
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DOI：
10.1016/j.bbagen.2013.04.032
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发表时间：
2013-08-01
影响因子：
3
通讯作者：
Sastry, Thotapalli P.
中科院分区：
文献类型：
--
作者：
Vedakumari, Weslen S.;Prabu, Periyathambi;Sastry, Thotapalli P.
背景：已经提出了几个问题，强调金属纳米颗粒对生物系统的有害毒性作用。寻找具有良好生物相容性和生物利用度的生物纳米颗粒可以解决这一问题。方法：采用新工艺制备纤维蛋白纳米颗粒（FNP），并对其理化性质进行表征。体外研究检测了FNP的细胞毒性和细胞摄取。通过(i)体外估计补体分裂产物C3a和C4d的产生以及（ii）体内促炎细胞因子、tnf - α、IL-1和IL-6的表达来研究FNP的先天免疫反应。通过静脉给药fitc标记的FNP在小鼠体内的生物分布研究。结果：FNP呈球形，粒径为25 ~ 28 nm。体外研究证明了纳米颗粒的生物相容性，它们分布在处理细胞的细胞质和细胞核中。补体活化研究显示，与阳性对照相比，C3a水平无显著升高。RT-PCR结果显示，FNP给药6小时后，tnf - α显著上调，IL-6细胞因子显著下调。体内生物分布研究显示，血液循环时间适中，纳米颗粒主要分布在肝脏，其次是肺、肾和脾。血液学、血清生化和组织病理学分析表明，FNP是无毒的。结论：FNP具有体积小、成本低、制备方便、生物相容性好等优点，是一种很有前途的新型给药材料。一般意义：我们的研究结果证明了FNP在生物医学应用中的安全性和前景。(C) 2013 Elsevier B.V.版权所有
Background: Several issues have been raised emphasizing the harmful toxic effects of metal nanoparticles towards biological systems. Search of biological nanoparticles with excellent biocompatibility and bioavailability could address this problem.Methods: Fibrin nanoparticles (FNP) were prepared using a novel technique and characterized for their physico-chemical properties. In vitro studies were performed to examine cytotoxicity and cellular uptake of FNP. Innate immune response to FNP was studied by (i) estimating in vitro generation of complement split products, C3a and C4d and (ii) in vivo expression of pro-inflammatory cytokines, TNF-alpha, IL-1 and IL-6. In vivo biodistribution study was carried out by intravenous administration of FITC-labelled FNP in mice.Results: FNP were spherical with size ranging from 25 to 28 nm. In vitro studies proved the biocompatibility of the nanoparticles, with their distribution across the cytoplasm and nucleus of treated cells. Complement activation studies showed insignificant increase in the level of C3a when compared with positive control. RT-PCR results revealed significant upregulation of TNF-alpha and downregulation of IL-6 cytokines after 6 h of FNP administration. In vivo biodistribution studies showed moderate blood circulation time, with predominant distribution of nanoparticles in the liver followed by the lungs, kidney and spleen. Haematology, serum biochemistry, and histopathology analyses demonstrated that FNP were non-toxic.Conclusion: Owing to their small size, low cost, ease of preparation and excellent biocompatibility, FNP might be a promising novel material for drug delivery applications.General significance: Our results demonstrate the safe and promising use of FNP for biomedical applications. (C) 2013 Elsevier B.V. All rights reserved.