Gratton Stephanie E A, Pohlhaus Patrick D, Lee Jin, Guo Ji, Cho Moo J, Desimone Joseph M
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Control Release. 2007 Aug 16;121(1-2):10-8. doi: 10.1016/j.jconrel.2007.05.027. Epub 2007 Jun 2.
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 (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 [(125)I]-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.
本文描述了一种制备尺寸在几十纳米到几微米之间的聚合物颗粒的新方法。这种称为PRINT（非湿润模板中的颗粒复制）的压印光刻技术利用了由低表面能全氟聚醚网络构成的弹性体模具的独特性能，能够从多种有机前体生产单分散、形状特定的纳米颗粒。与构建传统纳米颗粒（如脂质体、树枝状聚合物和胶体沉淀物）相比，这种颗粒生产的工程化性质具有许多优势。PRINT温和的“自上而下”方法能够同时且独立地控制颗粒的大小和形状、组成以及表面功能，并允许装载诸如有机小分子治疗药物和生物大分子等精细货物。因此，这一单一工具可作为一个全面的平台，用于合理设计和研究医学中的新型纳米载体，其应用范围涵盖从治疗到先进诊断等领域。进行了初步的体外和体内研究，证明了PRINT颗粒作为纳米医学中的递送载体的未来应用价值。使用PRINT方法制备了单分散的基于聚乙二醇（PEG）的200 nm颗粒，并通过扫描电子显微镜和动态光散射进行了表征。与HeLa细胞孵育显示，即使在高浓度下，细胞毒性也非常小。在健康小鼠经尾静脉推注给予[(125)I]标记的颗粒后，研究了其生物分布和药代动力学。颗粒主要分布在肝脏和脾脏，表观分布半衰期约为17分钟，随后是半衰期为3.3小时的缓慢再分布。发现中央和外周隔室的分布容积分别约为3 mL和5 mL。
