Herein we describe a formulation of self-encapsulating poly(lactic-co-glycolic acid) (PLGA) microspheres for vaccine delivery. Self-healing encapsulation is a novel encapsulation method developed by our group that enables the aqueous loading of large molecules into premade PLGA microspheres. Calcium phosphate (CaHPO₄) adjuvant gel was incorporated into the microspheres as a protein-trapping agent for improved encapsulation of antigen. Microspheres were found to have a median size of 7.05 ± 0.31 μm, with a w/w loading of 0.60 ± 0.05% of ovalbumin (OVA) model antigen. The formulation demonstrated continuous release of OVA over a 49-day period. Released OVA maintained its antigenicity over the measured period of >21 days of release. C57BL/6 mice were immunized via the intranasal route with prime and booster doses of OVA (10 μg) loaded into microspheres or coadministered with cholera toxin B (CTB), the gold standard of mucosal adjuvants. Microspheres generated a Th2-type response in both serum and local mucosa, with IgG antibody responses approaching those generated by CTB. The results suggest that this formulation of self-encapsulating microspheres shows promise for further study as a vaccine delivery system.

中文翻译：

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自包封的聚（乳酸-共-glycolic乙酸）（PLGA）微球用于鼻内疫苗递送

在本文中，我们描述了用于疫苗递送的自封装聚（乳酸-共-乙醇酸）（PLGA）微球的制剂。自修复封装是我们小组开发的一种新颖的封装方法，可以将大分子以水性方式装载到预制的PLGA微球中。磷酸钙（CaHPO ₄将佐剂凝胶作为蛋白质捕获剂掺入微球中，以改善抗原的封装。发现微球的中值大小为7.05±0.31μm，w / w载量为卵清蛋白（OVA）模型抗原的0.60±0.05％。该制剂显示在49天的时间内OVA持续释放。所释放的OVA在超过21天的释放的测量时间内保持了其抗原性。C57BL / 6小鼠通过鼻内途径免疫，接种至微球中或与黏膜佐剂黄金标准霍乱毒素B（CTB）共同给药，并接种了初次和加强剂量的OVA（10μg）。微球在血清和局部粘膜中均产生Th2型应答，IgG抗体应答接近CTB产生的应答。