Coombes A G, Tasker S, Lindblad M, Holmgren J, Hoste K, Toncheva V, Schacht E, Davies M C, Illum L, Davis S S
Department of Pharmaceutical Sciences, University of Nottingham, University Park, UK.
Biomaterials. 1997 Sep;18(17):1153-61. doi: 10.1016/s0142-9612(97)00051-3.
Poly(ethylene glycol)-dextran (PEG-DEX) conjugates have been used as a combined stabilizer and surface modifier to produce resorbable poly(DL-lactide-co-glycolide) (PLG) microparticles by an emulsification/solvent evaporation technique. The use of PEG or dextran polymers alone was incapable of producing microparticles. Particle size measurements revealed smaller mean particle sizes (480 nm) and improved polydispersity when using a 1.2% PEG substituted conjugate relative to a 9% substituted material (680 nm). PLG microparticles modified by post-adsorbed PEG-DEX conjugates flocculated in 0.01 M salt solutions, whereas PLG microparticles prepared using PEG-DEX as a surfactant were stable in at least 0.5 M NaCl solutions. Surface modification of PLG microparticles was confirmed by zeta potential measurements and surface analysis using X-ray photoelectron spectroscopy. The presence of surface exposed dextran was confirmed by an immunological detection method using a dextran-specific antiserum in an enzyme-linked immunosorbent assay. The findings support a model in which the PEG component of the PEG-DEX conjugate provides an anchor to the microparticle surface while the dextran component extends from the particle surface to contribute a steric stabilization function. This approach offers opportunities for attaching hydrophilic species such as targeting moieties to biodegradable microparticles to improve the interaction of drug carriers and vaccines with specific tissue sites.
聚乙二醇-葡聚糖（PEG-DEX）缀合物已被用作一种联合稳定剂和表面改性剂，通过乳化/溶剂蒸发技术来制备可吸收的聚（DL-丙交酯-共-乙交酯）（PLG）微粒。单独使用PEG或葡聚糖聚合物无法制备微粒。粒度测量结果显示，相对于9%取代材料（680 nm），使用1.2% PEG取代的缀合物时平均粒径更小（480 nm）且多分散性得到改善。经后吸附PEG-DEX缀合物改性的PLG微粒在0.01 M盐溶液中会絮凝，而使用PEG-DEX作为表面活性剂制备的PLG微粒在至少0.5 M NaCl溶液中是稳定的。通过ζ电位测量和使用X射线光电子能谱的表面分析证实了PLG微粒的表面改性。在酶联免疫吸附测定中使用葡聚糖特异性抗血清的免疫检测方法证实了表面存在暴露的葡聚糖。这些发现支持了一种模型，即PEG-DEX缀合物的PEG组分在微粒表面提供一个锚定，而葡聚糖组分从微粒表面延伸以发挥空间稳定功能。这种方法为将亲水性物质（如靶向部分）连接到可生物降解微粒上提供了机会，以改善药物载体和疫苗与特定组织部位的相互作用。
