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酸化蔗糖八硫酸酯包被壳聚糖衍生物纳米粒作为口服疫苗佐剂递药系统,可增强黏膜和系统免疫。

Acidified sucralfate encapsulated chitosan derivative nanoparticles as oral vaccine adjuvant delivery enhancing mucosal and systemic immunity.

机构信息

Zhejiang Provincial Key Laboratory of Plant Evolutionary Ecology and Conservation, Taizhou Key Laboratory of Biomedicine and Advanced Dosage Forms, School of Life Sciences, Taizhou University, Zhejiang, Taizhou 318000, China.

School of Medical Technology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, China.

出版信息

Int J Biol Macromol. 2024 Nov;279(Pt 3):135424. doi: 10.1016/j.ijbiomac.2024.135424. Epub 2024 Sep 7.

DOI:10.1016/j.ijbiomac.2024.135424
PMID:39245128
Abstract

Oral vaccines are generally perceived to be safe, easy to administer, and have the potential to induce both systemic and mucosal immune responses. However, given the challenges posed by the harsh gastrointestinal environment and mucus barriers, the development of oral vaccines necessitates the employment of a safe and efficient delivery system. In recent years, nanoparticle-based delivery has proven to be an ideal delivery vector for the manufacture of oral vaccines. Hence, considering the above, the sucralfate acidified (SA) encapsulated N-2-Hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC)/N,O-carboxymethyl chitosan (CMCS) nanoparticles (SA@N-2-HACC/CMCS NPs) were prepared, and the BSA was used as a model antigen to investigate the immune responses. The SA@N-2-HACC/CMCS NPs had a particle size of 227 ± 7.0 nm and a zeta potential of 8.43 ± 2.62 mV. The NPs displayed slow and sustained release and high stability in simulated gastric juice and intestinal fluid. RAW 264.7 macrophage-like cell line demonstrated enhanced uptake of the SA@N-2-HACC/CMCS/BSA Nps. The vaccine via oral administration markedly enhanced the residence time of BSA in the intestine for more than 12 h and elicited the production of IgG and sIgA. The SA@N-2-HACC/CMCS NPs developed here for oral administration is an excellent technique for delivering antigens and provides a path of mucosal vaccine research.

摘要

口服疫苗通常被认为是安全、易于管理的,并且具有诱导全身和黏膜免疫应答的潜力。然而,鉴于胃肠道环境和黏液屏障的严峻挑战,口服疫苗的开发需要使用安全有效的递送系统。近年来,基于纳米粒子的递送已被证明是制造口服疫苗的理想递送载体。因此,考虑到上述情况,制备了硫酸铝酸化(SA)包封的 N-2-羟丙基三甲基氯化铵壳聚糖(N-2-HACC)/N,O-羧甲基壳聚糖(CMCS)纳米颗粒(SA@N-2-HACC/CMCS NPs),并以牛血清白蛋白(BSA)作为模型抗原来研究免疫应答。SA@N-2-HACC/CMCS NPs 的粒径为 227 ± 7.0nm,zeta 电位为 8.43 ± 2.62mV。这些纳米颗粒在模拟胃液和肠液中具有缓慢而持续的释放和高稳定性。RAW 264.7 巨噬细胞样细胞系显示出对 SA@N-2-HACC/CMCS/BSA Nps 的摄取增强。通过口服给予疫苗可显著延长 BSA 在肠道中的停留时间超过 12h,并引发 IgG 和 sIgA 的产生。这里开发的用于口服给药的 SA@N-2-HACC/CMCS NPs 是一种递送抗原的优秀技术,为黏膜疫苗研究提供了一种途径。

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