Novel chitosan particles and chitosan-coated emulsions inducing immune response via intranasal vaccine delivery

Novel chitosan particles and chitosan-coated emulsions inducing immune response via intranasal vaccine delivery
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DOI:
10.1023/b:pham.0000022414.17183.58
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发表时间:
2004-04-01
影响因子:
3.7
通讯作者:
Maitani, Y
Maitani, Y
中科院分区:
医学3区
文献类型:
--
作者:
Nagamoto, T;Hattori, Y;Maitani, Y

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目的.本研究的目的是制备一种新型的疫苗载体微粒系统(纳米粒和乳剂)与壳聚糖和评价该系统对免疫应答的影响鼻内递送。通过改进乙醇注射法和改进的方法分别制备了壳聚糖纳米粒(NP)和壳聚糖包被乳剂(CC-Emul)。将吸附有卵清蛋白(OVA)和霍乱毒素(CT)的颗粒经鼻内(i.n.)和腹膜内(i. p.)administration.Results. NP和CC-Emul可以制备为粒径为约0.4 μ m至3 μ m。i.n. NP与i. p.,和i.n. 0.4 μ m-和1 μ m-大小的NP显著高于对照(OVA和CT)。伊加2 μ m大小的CC-Emul的细胞数显著高于对照组。采用简单的制备方法制备的新型壳聚糖颗粒表现出较高的OVA吸附性能。鼻内给药时,NP和CC-Emul诱导大鼠全身免疫应答。这些发现表明,CC-Emul和较小尺寸(0.4 μ m)的NP在鼻疫苗递送中对于靶向鼻相关淋巴组织(NALT)是有效的。
Purpose. The aim of this study was to prepare a novel vaccine carrier particulate system (nanoparticles and emulsions) with chitosan and to evaluate the effect of this system on the immune response for intranasal delivery.Methods. Chitosan nanoparticles (NP) and chitosan-coated emulsions (CC-Emul) were prepared by improvement of the method previously reported and by modified ethanol injection methods, respectively. The rats were immunized with the particles adsorbed with ovalbumin ( OVA) and cholera toxin (CT) by intranasal (i.n.) and intraperitoneal (i.p.) administration.Results. NP and CC-Emul could be prepared with particle diameter from about 0.4 mum to 3 mum. IgG induced by i.n. of NP was comparable with that by i.p., and IgA induced by i.n. of 0.4-mum- and 1-mum-size NP was significantly higher than control ( OVA and CT). IgG and IgA induced by i.n. of 2-mum-size CC-Emul were significantly higher than those with control.Conclusions. The novel chitosan particles used simple preparation methods showed high OVA adsorption. When administered intranasally, NP and CC-Emul induced systemic immune response in rats. These findings suggested that CC-Emul and the smaller-size (0.4 mum) NP are effective for targeting to nasal-associated lymphoid tissues (NALTs) in nasal vaccine delivery.