Mosafer Jafar, Sabbaghi Amir-Hossein, Badiee Ali, Dehghan Solmaz, Tafaghodi Mohsen
Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran.
School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Asian J Pharm Sci. 2019 Mar;14(2):216-221. doi: 10.1016/j.ajps.2018.04.005. Epub 2018 May 10.
For efficient mucosal vaccine delivery, nanoparticulate antigens are better taken by microfold cells in the nasal associated lymphoid tissue and also dendritic cells. Nanoparticles based on polymers such as chitosan (CHT) and its water soluble derivative, trimethylchitosan (TMC), could be successfully used as carrier/adjuvant for this purpose. Sodium alginate, a negatively charged biopolymer, could modify the immunostimulatory properties of CHT and TMC NPs and increase their stability. Sodium alginate (ALG)-coated chitosan (CHT) and trimethylchitosan (TMC) nanoparticles (NPs) loaded with inactivated PR8 influenza virus were successfully prepared by direct coating of the virus with CHT or TMC polymers to evaluate their immunoadjuvant potential after nasal immunization. After nasal immunizations in BALB/c mice, PR8-CHT formulation elicited higher IgG2a and IgG1 antibody titers compared with PR8-TMC. ALG coating of this formulation (PR8-CHT-ALG) significantly decreased the antibody titers and a less immune response was induced than PR8-TMC-ALG formulation. PR8-TMC-ALG formulation showed significantly higher IgG2a/IgG1 ratio, as criteria for Th1-type immune response, compared with PR8-CHT-ALG and PR8 virus alone. Altogether, the PR8-TMC-ALG formulation could be considered as an efficient intranasal antigen delivery system for nasal vaccines.
为实现高效的黏膜疫苗递送,纳米颗粒抗原更容易被鼻相关淋巴组织中的微褶细胞以及树突状细胞摄取。基于壳聚糖(CHT)及其水溶性衍生物三甲基壳聚糖(TMC)等聚合物的纳米颗粒可成功用作此目的的载体/佐剂。海藻酸钠是一种带负电荷的生物聚合物,可改变CHT和TMC纳米颗粒的免疫刺激特性并提高其稳定性。通过用CHT或TMC聚合物直接包被灭活的PR8流感病毒,成功制备了负载该病毒的海藻酸钠(ALG)包被的壳聚糖(CHT)和三甲基壳聚糖(TMC)纳米颗粒(NPs),以评估其经鼻免疫后的免疫佐剂潜力。在对BALB/c小鼠进行鼻内免疫后,与PR8-TMC相比,PR8-CHT制剂引发了更高的IgG2a和IgG1抗体滴度。该制剂(PR8-CHT-ALG)的ALG包被显著降低了抗体滴度,且诱导的免疫反应比PR8-TMC-ALG制剂弱。与PR8-CHT-ALG和单独的PR8病毒相比,PR8-TMC-ALG制剂作为Th1型免疫反应的标准,显示出显著更高的IgG2a/IgG1比值。总之,PR8-TMC-ALG制剂可被视为一种用于鼻用疫苗的高效鼻内抗原递送系统。