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用于生物医学应用的高纯度聚-γ-谷氨酸的生物合成。

Biosynthesis of highly pure poly-γ-glutamic acid for biomedical applications.

机构信息

INEB-Instituto de Engenharia Biomédica, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180, Porto, Portugal.

出版信息

J Mater Sci Mater Med. 2012 Jul;23(7):1583-91. doi: 10.1007/s10856-012-4639-x. Epub 2012 Apr 25.

Abstract

The remarkable properties of poly-aminoacids, mainly their biocompatibility and biodegradability, have prompted an increasing interest in these polymers for biomedical applications. Poly-γ-glutamic acid (γ-PGA) is one of the most interesting poly-aminoacids with potential applications as a biomaterial. Here we describe the production and characterization of γ-PGA by Bacillus subtilis natto. The γ-PGA was produced with low molecular weight (10-50 kDa), high purity grade (>99 %) and a D: -/L: -glutamate ratio of 50-60/50-40 %. To evaluate the feasibility of using this γ-PGA as a biomaterial, chitosan (Ch)/γ-PGA nanoparticles were prepared by the coacervation method at pH ranging from 3.0 to 5.0, with dimensions in the interval 214-221 nm with a poly-dispersion index of ca. 0.2. The high purity of γ-PGA produced by this method, which is firstly described here, renders this biopolymer suitable for biomedical applications. Moreover, the Ch/γ-PGA nanocomplexes developed in this investigation can be combined with biologically active substances for their delivery in the organism. The fact that the assembly between Ch and γ-PGA relies on electrostatic interactions enables addition of other molecules that can be released into the medium through changes from acidic to physiological pH, without loss in biological activity.

摘要

聚氨基酸具有显著的特性,主要包括生物相容性和可生物降解性,这促使人们越来越关注这些聚合物在生物医学领域的应用。γ-聚谷氨酸(γ-PGA)是最具应用潜力的聚氨基酸之一,可用作生物材料。本文描述了纳豆芽孢杆菌生产和特性γ-PGA。γ-PGA 的分子量低(10-50 kDa),纯度高(>99%),D:-/L:-谷氨酸比例为 50-60/50-40%。为评估将这种 γ-PGA 用作生物材料的可行性,我们采用共凝聚法在 pH 值为 3.0-5.0 的范围内制备壳聚糖(Ch)/γ-PGA 纳米颗粒,其粒径在 214-221nm 之间,多分散指数约为 0.2。本文首次描述了这种方法生产的 γ-PGA 具有高纯度,适用于生物医学应用。此外,本研究中开发的 Ch/γ-PGA 纳米复合物可以与生物活性物质结合,用于在体内的递药。壳聚糖与 γ-PGA 之间的组装依赖于静电相互作用,这使得可以添加其他分子,这些分子可以通过从酸性到生理 pH 的变化释放到介质中,而不会失去生物活性。

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