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采用离子凝胶法制备带负电荷的壳聚糖纳米粒子,用于包裹带正电荷的蛋白质。

Negatively charged chitosan nanoparticles prepared by ionotropic gelation for encapsulation of positively charged proteins.

机构信息

Laboratory of Automatic Control, Chemical and Pharmaceutical Engineering (LAGEPP), University Claude Bernard Lyon 1, 69622 Villeurbanne, France; Federal University of Paraná (UFPR), 80210-170 Curitiba, Brazil.

Federal University of Paraná (UFPR), 80210-170 Curitiba, Brazil.

出版信息

Int J Pharm. 2023 Jul 25;642:123164. doi: 10.1016/j.ijpharm.2023.123164. Epub 2023 Jun 24.

DOI:10.1016/j.ijpharm.2023.123164
PMID:37356507
Abstract

The nanoprecipitation of hydrogel nanoparticles by complex coacervation is investigated through a systematic study of the popular chitosan-polyphosphate pair of polyelectrolytes with opposite charges at pH 4. Polyphosphates of varying molar masses and electrical charges are investigated as alternatives to the commonly used tripolyphosphate, so as to assess the influence of the strength of electrostatic interactions on the fabrication possibility, the size of hydrogel particles, and their overall charge. Sodium hexametaphosphate and sodium polyphosphate allow the manufacture of such nanoparticles with either a positive or a negative charge, depending on the chitosan/polyphosphate ratio and the order of mixing. The classical way of mixing by pouring the polyphosphate solution into the chitosan solution yields microparticles. Inverting the order of mixing by pouring the chitosan solution into the polyphosphate solution allows the precipitation of negatively charged nanoparticles with diameters in the range 100-200 nm. Such charge inversion of the chitosan into negative is not possible with the common TPP. It was achieved using sodium hexametaphosphate and sodium polyphosphate having a larger negative charge. Charge inversion of chitosan allows an efficient encapsulation of positively charged proteins with an improved encapsulation efficiency than in the usual TPP-based coacervate. The encapsulation of the bovine serum albumin at pH 4 is given as a case study of a positively charged protein.

摘要

通过系统研究具有相反电荷的流行的壳聚糖-聚磷酸盐对聚电解质,研究了通过复凝聚作用纳米沉淀水凝胶纳米粒子。研究了具有不同摩尔质量和电荷的多磷酸盐作为常用三聚磷酸盐的替代品,以评估静电相互作用的强度对制造可能性、水凝胶颗粒的大小及其整体电荷的影响。六偏磷酸钠和多聚磷酸钠允许根据壳聚糖/多磷酸盐的比例和混合顺序制造带正电荷或负电荷的此类纳米粒子。通过将多磷酸盐溶液倒入壳聚糖溶液中进行混合的经典方法得到微球。通过将壳聚糖溶液倒入多磷酸盐溶液中颠倒混合顺序,允许沉淀带负电荷的纳米粒子,其直径在 100-200nm 范围内。使用具有较大负电荷的六偏磷酸钠和多聚磷酸钠,可以将壳聚糖的这种电荷反转成负电荷,而不是使用常见的 TPP。通过反转混合顺序,在通常的基于 TPP 的凝聚物中,带正电荷的蛋白质的包封效率得到提高,从而可以有效地包封带正电荷的蛋白质。以牛血清白蛋白在 pH4 下的包封为例,研究了带正电荷的蛋白质。

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