Owens Donald E, Peppas Nicholas A
Department of Chemical Engineering, University of Texas at Austin, 1 University Station, C0400, Austin, TX 78712, USA.
Int J Pharm. 2006 Jan 3;307(1):93-102. doi: 10.1016/j.ijpharm.2005.10.010. Epub 2005 Nov 21.
The process of opsonization is one of the most important biological barriers to controlled drug delivery. Injectable polymeric nanoparticle carriers have the ability to revolutionize disease treatment via spatially and temporally controlled drug delivery. However, opsonin proteins present in the blood serum quickly bind to conventional non-stealth nanoparticles, allowing macrophages of the mononuclear phagocytic system (MPS) to easily recognize and remove these drug delivery devices before they can perform their designed therapeutic function. To address these limitations, several methods have been developed to mask or camouflage nanoparticles from the MPS. Of these methods, the most preferred is the adsorption or grafting of poly(ethylene glycol) (PEG) to the surface of nanoparticles. Addition of PEG and PEG-containing copolymers to the surface of nanoparticles results in an increase in the blood circulation half-life of the particles by several orders of magnitude. This method creates a hydrophilic protective layer around the nanoparticles that is able to repel the absorption of opsonin proteins via steric repulsion forces, thereby blocking and delaying the first step in the opsonization process.
调理作用过程是可控药物递送最重要的生物屏障之一。可注射的聚合物纳米颗粒载体有能力通过空间和时间上可控的药物递送彻底改变疾病治疗方式。然而,血清中存在的调理素蛋白会迅速结合到传统的非隐形纳米颗粒上,使得单核吞噬系统(MPS)的巨噬细胞能够在这些药物递送装置发挥其设计的治疗功能之前轻易识别并清除它们。为了解决这些局限性,已经开发了几种方法来使纳米颗粒对MPS进行屏蔽或伪装。在这些方法中,最优选的是将聚乙二醇(PEG)吸附或接枝到纳米颗粒表面。在纳米颗粒表面添加PEG和含PEG的共聚物会使颗粒的血液循环半衰期增加几个数量级。这种方法在纳米颗粒周围形成一层亲水性保护层,该保护层能够通过空间排斥力排斥调理素蛋白的吸附,从而阻断并延迟调理作用过程的第一步。