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Preparation, characterization and in vivo evaluation of alginate-coated chitosan and trimethylchitosan nanoparticles loaded with PR8 influenza virus for nasal immunization

机译:海藻酸钠包被的壳聚糖和三甲基壳聚糖纳米粒的制备,表征及体内评价

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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.
机译:为了有效地递送粘膜疫苗,鼻相关淋巴组织以及树突状细胞中的微折叠细胞可以更好地吸收纳米颗粒抗原。基于聚合物如壳聚糖(CHT)及其水溶性衍生物三甲基壳聚糖(TMC)的纳米颗粒可成功用作此目的的载体/佐剂。海藻酸钠,一种带负电荷的生物聚合物,可以改变CHT和TMC NP的免疫刺激特性,并增加其稳定性。通过经CHT或TMC聚合物直接包被以评估其在鼻免疫后的免疫佐剂潜力,成功制备了载有灭活PR8流感病毒的海藻酸钠(ALG)包被的壳聚糖(CHT)和三甲基壳聚糖(TMC)纳米颗粒(NPs)。在BALB / c小鼠中进行鼻腔免疫后,PR8-CHT制剂引起的PR2-IgG和IgG1抗体滴度高于PR8-TMC。与PR8-TMC-ALG制剂相比,该制剂的ALG涂层(PR8-CHT-ALG)显着降低了抗体效价,并诱导了更少的免疫应答。与单独使用PR8-CHT-ALG和PR8病毒相比,PR8-TMC-ALG制剂显示出明显更高的IgG2a / IgG1比,作为Th1型免疫应答的标准。总之,PR8-TMC-ALG制剂可以被认为是用于鼻疫苗的有效鼻内抗原递送系统。

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