In vitro evaluation of novel (nanoparticle) oral delivery systems allow selection of gut immunomodulatory formulations
In vitro evaluation of novel (nanoparticle) oral delivery systems allow selection of gut immunomodulatory formulations
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新型（纳米颗粒）口服给药系统的体外评估允许选择肠道免疫调节制剂
DOI：
10.1016/j.fsi.2021.03.007
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发表时间：
2021
影响因子：
4.7
通讯作者：
Attaya A
中科院分区：
文献类型：
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作者：
Attaya A
口服递送是对养殖鱼类进行疫苗接种的最方便的方式，然而它仍然是有问题的，主要是由于缺乏商业上有效的疫苗载体来保护抗原免受胃降解并确保其从肠道摄取。为了提高口服疫苗的潜力，本研究评估了一种新型硅纳米颗粒载体（VacSaf载体）。使用不同的制备方法用VacSaf载体配制杀鲑气单胞菌抗原以产生干粉和液体制剂。12种制剂首先进行体外评价，其中A.与A.单独的杀鲑素杆菌素。这在暴露于酸性条件以模拟胃加工后尤其明显。使用两个剂量和两个给药方案（5天vs 10天，后者给药5天，停药5天，给药5天）将一种制剂（FD 1）进行口服递送，并通过qPCR评估肠（幽门盲囊、中肠和后肠）和脾中免疫基因的转录物变化，并通过ELISA测量血清IgM。单独的VacSaf载体被证明在体内使用是安全的，因为没有看到副作用，但它确实诱导一些细胞因子的表达，并且可能具有作为口服佐剂候选物的价值。与A.单独的杀鲑素杆菌素（几乎没有效果），并证实了在适当的口服疫苗接种后该肠道区域的免疫能力。这些结果表明，体外筛选口服给药制剂具有价值，可用于评估最有前途的制剂，以进一步测试。
Oral delivery is the most convenient way to vaccinate cultured fish, however it is still problematic, primarily due to a lack of a commercially valid vaccine vehicle to protect the antigen against gastric degradation and ensure its uptake from the intestine. With the goal of advancing the potential to vaccinate orally, this study evaluates a novel silicon nanoparticle-based vehicle (VacSaf carrier). Aeromonas salmonicida antigens were formulated with the VacSaf carrier using different preparation methods to generate dry powder and liquid formulations. Twelve formulations were first subjected to anin vitroevaluation where theA. salmonicidabacterin conjugated to VacSaf carriers were found superior at inducing pro-inflammatory cytokine expression in primary leucocyte cultures and the macrophage/monocyte cell line RTS-11 compared withA. salmonicidabacterin alone. This was especially apparent after exposure to acid conditions to mimic stomach processing. One formulation (FD1) was taken forward to oral delivery using two doses and two administration schedules (5 days vs 10 days, the latter 5 days on, 5 days off, 5 days on), and the transcript changes of immune genes in the intestine (pyloric caeca, midgut and hindgut) and spleen were evaluated by qPCR and serum IgM was measured by ELISA. The VacSaf carrier alone was shown to be safe for usein vivo, in that no side-effects were seen, but it did induce expression of some cytokines, and may have value as an oral adjuvant candidate. The FD1 bacterin formulation was effective at inducing a range of cytokines associated with innate and adaptive immunity, mainly in the pyloric caeca, compared toA. salmonicidabacterin alone (which had almost no effect), and confirms the immune competence of this gut region following appropriate oral vaccination. These results reveal thatin vitroscreening of formulations for oral delivery has value and can be used to assess the most promising formulations to test further.