Xu Shuwen, Feng Zi'an, Zhang Yue, Ni Haiyu, Liu Zhenguang, Wang Deyun
Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.
Institute of Traditional Chinese Veterinary Medicine, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China.
Int J Biol Macromol. 2022 Dec 1;222(Pt B):1936-1947. doi: 10.1016/j.ijbiomac.2022.09.283. Epub 2022 Oct 3.
Modern medical science believes that astragalus polysaccharides (APS) have the efficacy of strengthening immune system, while their peculiarities greatly reduced clinical applications. Poly(lactic-co-glycolic acid) (PLGA) is a synthetic carrier material with outstanding biochemical properties. In this study, PLGA materials were used to prepare the novel pH-responsive targeting drug delivery carriers which were encapsulated APS inside. The OVA-loaded pH-responsive APS-encapsulated PLGA Nanoparticles (OVA-loaded pH-responsive APSPs) and the OVA-loaded APSPs were constructed by multiple emulsion solvent evaporation method. Characterization and immunoenhancing activities of PLGA nanoparticles (NPs) were evaluated in vitro and in vivo. The size of NPs ranged from 142.6 to 194.6 nm, and all NPs were negatively charged. Additionally, pH-responsive APSPs shown violent release behaviors in an acidic environment. pH-responsive APSPs had low cytotoxicity, and significantly enhanced expression of MHC-II, CD80, CD86, and phagocytosis ability of macrophages. Both OVA-loaded NPs could stimulate greater Th1-biased immune responses compared with APS alone, and they could significantly promote proliferation, differentiation, and maturity of splenic lymphocytes and dendritic cells in mice respectively. NPs induced significantly greater antigen-specific IgG antibody responses and expression of IL-4, IL-6, IFN-γ, and TNF-α. Moreover, OVA-loaded pH-responsive APSPs had an aptitude for both cellular and humoral immunity reinforcement during early immunization, while OVA-loaded APSPs had advantages on later stages of immune responses.
现代医学认为黄芪多糖（APS）具有增强免疫系统的功效，但其特性极大地限制了其临床应用。聚乳酸-羟基乙酸共聚物（PLGA）是一种具有优异生化特性的合成载体材料。在本研究中，采用PLGA材料制备了新型pH响应靶向药物递送载体，并将APS包裹在其中。通过复乳溶剂蒸发法构建了负载卵清蛋白（OVA）的pH响应性包裹APS的PLGA纳米颗粒（OVA负载的pH响应性APSPs）和OVA负载的APSPs。对PLGA纳米颗粒（NPs）进行了体外和体内表征及免疫增强活性评估。NPs的粒径范围为142.6至194.6nm，且所有NPs均带负电荷。此外，pH响应性APSPs在酸性环境中表现出剧烈的释放行为。pH响应性APSPs具有低细胞毒性，并显著增强了巨噬细胞MHC-II、CD80、CD86的表达及吞噬能力。与单独的APS相比，两种负载OVA的NPs均可刺激更强的Th1偏向性免疫反应，且它们可分别显著促进小鼠脾淋巴细胞和树突状细胞的增殖、分化和成熟。NPs诱导产生了显著更高的抗原特异性IgG抗体反应以及IL-4、IL-6、IFN-γ和TNF-α的表达。此外，OVA负载的pH响应性APSPs在早期免疫期间对细胞免疫和体液免疫增强均有作用，而OVA负载的APSPs在免疫反应后期具有优势。
