中文摘要：研究合成了一种疫苗佐剂和传递系统，由N-2-羟丙基三甲基氯化铵壳聚糖（N-2-HACC）和N，O-羧甲基壳聚糖（CMC）组成。采用聚电解质复合法分别合成了N-2-HACC-CMC/NDV/IBV纳米颗粒（NPs）和N-2-HACC-CMC/NDV-IBV NPs，这两种纳米颗粒细菌毒性低且稳定性好。将两种纳米颗粒在37°环境下贮存数周后，两种复合物都能继续维持其生物活性。体外试验表明，纳米化的疫苗能够持续释放NDV和IBV抗原。体外免疫结果表明，与商业化的灭活疫苗相比，鼻腔免疫N-2-HACC-CMC/NDV/IBV NPs 或 N-2-HACC-CMC/NDV-IBV NPs能够诱导产生更高水平的IgG和IgA抗体滴度，显著提高淋巴细胞的增殖能力，诱导产生更高水平的IL-2、IL-4和IFN-γ。结果表明，N-2-HACC-CMC可以作为粘膜免疫和粘膜给药的一种有效佐剂或传递载体进行应用，在制药领域应用前景广阔。
 
外文摘要：Newcastle disease (ND) and infectious bronchitis (IB) are important diseases, which cause respiratory diseases in chickens, resulting in severely economic losses in the poultry industry. In this study, N-2-hydroxypropyl trimethyl ammonium chloride chitosan (N-2-HACC) and N,O-carboxymethyl chitosan (CMC) were synthesized as adjuvant and delivery carrier for vaccine antigens. N-2-HACC-CMC/NDV/IBV nanoparticles (NPs) (NDV/La Sota and IBV/H120 encapsulated in N-2-HACC-CMC NPs) and N-2-HACC-CMC/NDV-IBV NPs (the mixing of N-2-HACC-CMC/NDV NPs and N-2-HACC-CMC/IBV NPs in a ratio of 1:1) were prepared by the polyelectrolyte composite method, respectively. Both nanoparticles exhibited lower cytotoxicity and higher stability. Their bioactivities were maintained when they were stored at 37 degrees C for three weeks. Release assay in vitro showed that both NDV and IBV could be sustainably released from the nanoparticles after an initial burst release. In vivo immunization of chickens showed that N-2-HACC-CMC/NDV/IBV NPs or N-2-HACC-CMC/NDV-IBV NPs intranasally induced higher titers of IgG and IgA antibodies, significantly promoted proliferation of lymphocytes and induced higher levels of interleukine-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma) than the commercially combined attenuated live vaccine did. This is the first study in the field of animal vaccines demonstrating that intranasal administration of chickens with antigens (NDV and IBV) encapsulated with chitosan derivative could induce humoral, cellular, and mucosal immune responses, which protected chickens from the infection of highly virulent NDV and IBV. This study indicated that N-2-HACC-CMC could be used as an efficient adjuvant and delivery carrier for further development of mucosal vaccines and drugs and could have an immense application potential in medicine.
外文关键词：Newcastle disease； infectious bronchitis； N-2-hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles； vaccine adjuvant； intranasal delivery
作者：Zhao, K; Li, SS; Li, W; Yu, L; Duan, XT; Han, JY; Wang, XH; Jin, Z
作者单位：黑龙江大学
期刊名称：DRUG DELIVERY
期刊影响因子：6.4
出版年份：2017
出版刊次：10
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