Department of Pharmaceutical Sciences, University of Padua, Via F. Marzolo, 5, 35131 Padua, Italy.
Int J Pharm. 2013 Jan 2;440(1):111-23. doi: 10.1016/j.ijpharm.2011.12.029. Epub 2011 Dec 24.
Translation of therapeutic proteins to pharmaceutical products is often encumbered by their inadequate physicochemical and biopharmaceutical properties, namely low stability and poor bioavailability. Over the last decades, several academic and industrial research programs have been focused on development of biocompatible polymers to produce appropriate formulations that provide for enhanced therapeutic performance. According to their physicochemical properties, polymers have been exploited to obtain a variety of formulations including biodegradable microparticles, 3-dimensional hydrogels, bioconjugates and soluble nanocomposites. Several soluble polymers bearing charges or hydrophobic moieties along the macromolecular backbone have been found to physically associate with proteins to form soluble nanocomplexes. Physical complexation is deemed a valuable alternative tool to the chemical bioconjugation. Soluble protein/polymer nanocomplexes formed by physical specific or unspecific interactions have been found in fact to possess peculiar physicochemical, and biopharmaceutical properties. Accordingly, soluble polymeric systems have been developed to increase the protein stability, enhance the bioavailability, promote the absorption across the biological barriers, and prolong the protein residence in the bloodstream. Furthermore, a few polymers have been found to favour the protein internalisation into cells or boost their immunogenic potential by acting as immunoadjuvant in vaccination protocols.
治疗性蛋白向药物产品的转化常常受到其理化和生物制药性质不足的限制，即低稳定性和差的生物利用度。在过去的几十年中，已经有几个学术和工业研究计划专注于开发生物相容性聚合物，以生产出适当的配方，从而提供增强的治疗性能。根据其理化性质，聚合物已被用于获得多种制剂，包括可生物降解的微球、3D 水凝胶、生物缀合物和可溶性纳米复合材料。已经发现许多带有电荷或疏水性部分的可溶性聚合物沿着聚合物主链与蛋白质物理结合形成可溶性纳米复合物。物理复合被认为是化学偶联的一种有价值的替代工具。事实上，通过物理特异性或非特异性相互作用形成的可溶性蛋白/聚合物纳米复合物具有独特的理化和生物制药性质。因此，已经开发出可溶性聚合物系统来提高蛋白质稳定性、增强生物利用度、促进穿过生物屏障的吸收，并延长蛋白质在血液中的停留时间。此外，一些聚合物已被发现通过在疫苗方案中作为免疫佐剂来促进蛋白质进入细胞内化或增强其免疫原性。
