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载免疫球蛋白 A 壳聚糖-葡聚糖硫酸酯纳米粒作为蛋白质抗原鼻腔给药系统的初步研究。

Preliminary studies on the development of IgA-loaded chitosan-dextran sulphate nanoparticles as a potential nasal delivery system for protein antigens.

机构信息

School of Pharmacy, CHIRI, Western Australia Biomedical Research Institute, Curtin University, GPO Box U1987, Perth, Western Australia 6845, Australia.

出版信息

J Microencapsul. 2013;30(3):283-94. doi: 10.3109/02652048.2012.726279. Epub 2012 Sep 21.

Abstract

This study describes the development of a biodegradable nanoparticulate system for the intranasal delivery of multiple proteins. Chitosan (CS)-dextran sulphate (DS) nanoparticles were developed and optimised for the incorporation of pertussis toxin (PTX) and a potential targeting ligand (immunoglobulin-A, IgA). In vitro characterization and in vivo uptake studies were performed for the evaluation of developed nanoparticles. The ratio of CS to DS, the order of mixing and pH of nanoparticle suspension were identified as important formulation factors governing the size and zeta potential of nanoparticles. An optimised CS-DS nanoparticle formulation prepared with the CS to DS weight ratio of 3 : 1 was used to load PTX and/or IgA. Entrapment efficiency of >90% was obtained for both. The in vivo uptake of IgA-loaded CS-DS nanoparticles in mice showed a preferential uptake of nanoparticles probably by nasal membranous or microfold cells following intranasal administration. The results of this study indicate the potential application of IgA-loaded CS-DS nanoparticles as a nasal vaccine delivery system.

摘要

本研究描述了一种可生物降解的纳米颗粒系统的开发,用于多种蛋白质的经鼻递药。壳聚糖 (CS)-葡聚糖硫酸盐 (DS) 纳米颗粒被开发并优化用于纳入百日咳毒素 (PTX) 和一种潜在的靶向配体 (免疫球蛋白-A,IgA)。进行了体外特性和体内摄取研究,以评估所开发的纳米颗粒。CS 与 DS 的比例、混合顺序和纳米颗粒悬浮液的 pH 被确定为控制纳米颗粒大小和zeta 电位的重要制剂因素。使用优化的 CS-DS 纳米颗粒制剂,CS 与 DS 的重量比为 3:1 来负载 PTX 和/或 IgA。两者的包封效率均>90%。经鼻给予后,载有 IgA 的 CS-DS 纳米颗粒在小鼠中的体内摄取显示出纳米颗粒的优先摄取,可能是通过鼻黏膜或微折叠细胞。本研究结果表明,载有 IgA 的 CS-DS 纳米颗粒作为鼻腔疫苗递送系统具有潜在的应用前景。

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