Nanofabricated particles for engineered drug therapies:: A preliminary Biodistribution study of PRINT ™ nanoparticles
Nanofabricated particles for engineered drug therapies:: A preliminary Biodistribution study of PRINT ™ nanoparticles
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DOI：
10.1016/j.jconrel.2007.05.027
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发表时间：
2007-08-16
影响因子：
10.8
通讯作者：
DeSimone, Joseph M.
中科院分区：
文献类型：
--
作者：
Gratton, Stephanie E. A.;PohhauS, Patrick D.;DeSimone, Joseph M.
描述了一种用于制造几十纳米至几微米量级的聚合物颗粒的新方法。这种称为PRINT（TM）（非润湿模板中的颗粒复制）的压印平版印刷技术利用了由低表面能全氟聚醚网络组成的弹性体模具的独特性质，允许从大量有机前体生产单分散、形状特定的纳米颗粒。颗粒生产的这种工程性质与传统纳米颗粒如脂质体、树枝状聚合物和胶体沉淀物的构建相比具有许多优点。PRINT温和的“自上而下”方法能够同时独立地控制颗粒尺寸和形状、组成和表面功能，并允许装载精细货物，如小的有机治疗剂和生物大分子。因此，这个单一的工具作为一个全面的平台，用于合理设计和研究新的纳米载体在医学上，具有从治疗到先进诊断的应用范围。进行了初步的体外和体内研究，证明了PRINT颗粒在纳米医学中作为递送载体的未来效用。单分散200 nm的聚（乙二醇）为基础的（PEG）粒子制造使用PRINT方法和其特征在于通过扫描电子显微镜和动态光散射。与HeLa细胞一起孵育显示出非常小的细胞毒性，即使在高浓度下。在健康小鼠尾静脉推注给药后，研究了[I-125]标记颗粒的生物分布和药代动力学。颗粒主要分布于肝脏和脾脏，表观分布t（1/2）约为17 min，随后缓慢再分布，t（1/2）为3.3 h。发现中央室和外周室的分布容积分别约为3 mL和5 mL。(C)2007 Elsevier B. V.保留所有权利。
A novel method for the fabrication of polymeric particles on the order of tens of nanometers to several microns is described. This imprint lithographic technique called PRINT (TM) (Particle Replication In Non-wetting Templates), takes advantage of the unique properties of elastomeric molds comprised of a low surface energy perfluoropolyether network, allowing the production of monodisperse, shape-specific nanoparticles from an extensive array of organic precursors. This engineered nature of particle production has a number of advantages over the construction of traditional nanoparticles such as liposomes, dendrimers, and colloidal precipitates. The gentle "top down" approach of PRINT enables the simultaneous and independent control over particle size and shape, composition, and surface functionality, and permits the loading of delicate cargos such as small organic therapeutics and biological macromolecules. Thus, this single tool serves as a comprehensive platform for the rational design and investigation of new nanocarriers in medicine, having applications ranging from therapeutics to advanced diagnostics. Preliminary in vitro and in vivo studies were conducted, demonstrating the future utility of PRINT particles as delivery vectors in nanomedicine. Monodisperse 200 nm poly(ethylene glycol)-based (PEG) particles were fabricated using PRINT methodology and characterized via scanning electron microscopy and dynamic light scattering. Incubation with HeLa cells showed very little cytotoxicity, even at high concentrations. The biodistribution and pharmacokinetics of [I-125]-labeled particles were studied in healthy mice following bolus tail vein administration. The particles were distributed mainly to the liver and the spleen with an apparent distribution t(1/2) of approximately 17 min followed by slow redistribution with a t(1/2) of 3.3 h. The volume of distribution for the central and peripheral compartments was found to be approximately 3 mL and 5 mL, respectively. (C) 2007 Elsevier B.V. All rights reserved.