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郝欣岩, 张远冬, 侯盈盈, 等. 壳聚糖修饰的纳米乳用于鼻腔疫苗递送的研究[J]. 四川大学学报(医学版), 2021, 52(4): 592-597. DOI: 10.12182/20210760104
引用本文: 郝欣岩, 张远冬, 侯盈盈, 等. 壳聚糖修饰的纳米乳用于鼻腔疫苗递送的研究[J]. 四川大学学报(医学版), 2021, 52(4): 592-597. DOI: 10.12182/20210760104
HAO Xin-yan, ZHANG Yuan-dong, HOU Ying-ying, et al. Applying Chitosan-Modified Nanoemulsion in Nasal Vaccine Delivery[J]. Journal of Sichuan University (Medical Sciences), 2021, 52(4): 592-597. DOI: 10.12182/20210760104
Citation: HAO Xin-yan, ZHANG Yuan-dong, HOU Ying-ying, et al. Applying Chitosan-Modified Nanoemulsion in Nasal Vaccine Delivery[J]. Journal of Sichuan University (Medical Sciences), 2021, 52(4): 592-597. DOI: 10.12182/20210760104

壳聚糖修饰的纳米乳用于鼻腔疫苗递送的研究

Applying Chitosan-Modified Nanoemulsion in Nasal Vaccine Delivery

  • 摘要:
      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  制备的壳聚糖修饰的纳米乳疫苗平均粒径为(167.2±0.75) nm,多分散系数为0.21±0.01,平均电位为(13.7±0.85) mV,对抗原的包封率为92.7%;该纳米乳疫苗稳定性良好,在犬肾上皮细胞上未表现出明显细胞毒性;在树突状细胞和犬肾上皮细胞上均显示了较高的摄取效率,分别为(49.7±3.45)%和(59.7±2.19)%。此外,阳离子纳米乳也显著增加了抗原在小鼠鼻腔的滞留时间,给药后60 min仍有较多纳米乳疫苗滞留于鼻腔;经小鼠鼻腔免疫后,与游离抗原和未经壳聚糖修饰的纳米乳疫苗比较,壳聚糖修饰的纳米乳疫苗诱导了较高的系统及黏膜抗体水平(P<0.01)。
      结论  本研究制备的壳聚糖修饰纳米乳能够增强鼻腔疫苗免疫效力,是一个具有较大潜力的鼻腔疫苗递送载体。

     

    Abstract:
      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.

     

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