壳聚糖修饰的纳米乳用于鼻腔疫苗递送的研究

目的 制备壳聚糖修饰的阳离子纳米乳,用于延长疫苗在鼻腔的滞留时间并提高细胞摄取效率,增强鼻腔疫苗免疫效力.方法 制备表面包裹壳聚糖的纳米乳疫苗;表征其粒径、电位和抗原包封率,考察其稳定性和细胞毒性;测定其在不同细胞上的摄取效率和小鼠鼻腔的滞留情况;最后对小鼠进行鼻腔免疫,检测小鼠血清和鼻腔灌洗液中抗体水平.结果 制备的...

Applying Chitosan-Modified Nanoemulsion in Nasal Vaccine Delivery

  Objective  To prepare a chitosan-modified cationic nanoemulsion that could be used to prolong the residence time of nasal vaccines in the nasal cavity and improve the cellular uptake efficiency so as to enhance the immune efficacy of nasal vaccines.  Methods  A nanoemulsion-based vaccine coated with chitosan was prepared, and the particle size, potential, antigen encapsulation efficiency, stability as well as cytotoxicity were examined. The uptake efficiency of vaccine on different cells and the residence time of vaccine in the nasal cavity were measured. Finally, nasal vaccine was administered on mice and the antibody levels in the serum and in the nasal lavage fluids of the immunized mice were examined.  Results  The nanoemulsion-based vaccine had an average particle size of (167.2±0.75) nm, a polydispersity index (PDI) of 0.21±0.01, and an average potential of (13.7±0.85) mV. The encapsulation efficiency of antigen was 92.7%. The nanoemulsion-based vaccine had good stability and did not show obvious cytotoxicity in Madin-Darby canine kidney (MDCK) epithelial cells. The vaccine demonstrated relatively high cellular uptake of antigens on DC2.4 and MDCK cells at (49.7±3.45)% and (59.7±2.19)%, respectively. Besides, the cationic nanoemulsion also significantly increased the residence time of the antigen, and a considerable amount of nanoemulsion-based vaccine was found remaining in the nasal cavity 60 minutes after administration. Compared with free antigen and the nanoemulsion without chitosan modification, the chitosan-modified nanoemulsion vaccine induced higher systemic and mucosal antibody levels in mice after nasal immunization (P<0.01).  Conclusion  The chitosan-modified nanoemulsion vaccine prepared in the study can enhance the immune efficacy of nasal vaccines, showing great potential to be used as a delivery carrier for nasal vaccines.