Betancourt Tania, Byrne James D, Sunaryo Nicole, Crowder Spencer W, Kadapakkam Meena, Patel Shefali, Casciato Shelly, Brannon-Peppas Lisa
Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas 78712, USA.
J Biomed Mater Res A. 2009 Oct;91(1):263-76. doi: 10.1002/jbm.a.32247.
This work evaluates various techniques for the incorporation of poly(ethylene glycol) (PEG) onto biodegradable nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA) or poly(lactic acid) (PLA) with the purpose of providing a functional site for surface conjugation of targeting agents and for improving surface properties. The techniques compared were based on NP preparation with blends of PLGA and poloxamer or with block copolymers of PLGA/PLA with PEG. Blending of PLGA with poloxamer 407 resulted in the incorporation of the latter to up to a 43 wt % content. Direct conjugation of heterofunctional NH2-PEG-COOH to the surface of premade NPs was not highly effective. Preparation of copolymers of PLGA with PEG was determined to be more effective and versatile by polymerization of lactide and glycolide dimers onto the hydroxyl group of heterofunctional OH-PEG-COOH than by conjugation of the premade polymers with carbodiimide chemistry. NPs prepared with these copolymers confirmed the surface localization of PEG and proved to be useful for conjugation of mouse immumoglobulin as a model targeting agent.
这项工作评估了多种将聚乙二醇（PEG）结合到聚乳酸-乙醇酸共聚物（PLGA）或聚乳酸（PLA）的可生物降解纳米颗粒（NP）上的技术，目的是为靶向剂的表面偶联提供一个功能位点，并改善表面性质。所比较的技术基于用PLGA与泊洛沙姆的混合物或PLGA/PLA与PEG的嵌段共聚物制备NP。PLGA与泊洛沙姆407混合后，后者的掺入量可达43 wt%。将异功能NH2-PEG-COOH直接偶联到预制NP的表面效果不佳。通过将丙交酯和乙交酯二聚体聚合到异功能OH-PEG-COOH的羟基上，制备PLGA与PEG的共聚物比用碳二亚胺化学方法将预制聚合物偶联更有效且更具通用性。用这些共聚物制备的NP证实了PEG的表面定位，并证明可用于偶联小鼠免疫球蛋白作为模型靶向剂。
