Department of Bioengineering, Faculty of Chemical and Metallurgical Engineering, Yildiz Technical University, İstanbul, Turkiye.
Vocational School of Health Sciences Services, Üsküdar University, İstanbul, Turkiye.
Colloids Surf B Biointerfaces. 2023 Aug;228:113421. doi: 10.1016/j.colsurfb.2023.113421. Epub 2023 Jun 20.
The development of novel vaccine formulations against tuberculosis is necessary to reduce the number of new cases worldwide. Polymeric nanoparticles offer great potential as antigen delivery and immunostimulant systems for such purposes. In the study, we have encapsulated the antigenic peptide epitope of ESAT-6 protein of M. tuberculosis into PLGA nanoparticles and coated these nanoparticles with the cationic polymer of quaternized poly(4-vinylpyridine) (QPVP) to obtain a positively charged system as a potential nasal vaccine prototype. The produced spherical nanoparticles had hydrodynamic diameters between 180 and 240 nm with a narrow size distribution. The non-coated nanoparticle exhibited a 3-phase in vitro release profile that was completed in more than 4 months. In this release study, 5% of the peptide was released in the first 6 h and the nanoparticle remained silent until the 70th day. Then, an additional 5% of the peptide was released in 45 days. After coating the nanoparticle with QPVP, the release periods and peptide amounts dramatically changed. The antigenic peptide-loaded nanoparticles coated with the polycation stimulated the macrophages in vitro to release more nitric oxide (NO) compared to the free peptide and non-coated nanoparticle, which reveals the immunostimulant activity of the produced nanoparticle systems. The produced non-coated nanoparticles with the prolonged pulsatile release of the antigenic peptide can be used in the development of single injection self-boosting vaccine formulations. By coating these nanoparticles, both the release profile and immunogenicity can be changed.
新型结核疫苗制剂的开发对于减少全球新发病例数量是必要的。聚合纳米颗粒在作为抗原递呈和免疫刺激系统方面具有巨大的潜力。在研究中，我们将结核分枝杆菌 ESAT-6 蛋白的抗原肽表位包封到 PLGA 纳米颗粒中，并将这些纳米颗粒用季铵化聚（4-乙烯基吡啶）（QPVP）的阳离子聚合物进行涂层，以获得一种带正电荷的系统，作为潜在的鼻用疫苗原型。所产生的球形纳米颗粒的水动力学直径在 180 至 240nm 之间，具有较窄的粒径分布。未涂层的纳米颗粒表现出 3 相体外释放曲线，超过 4 个月才完成释放。在该释放研究中，有 5%的肽在最初的 6 小时内释放，纳米颗粒保持沉默，直到第 70 天。然后，在 45 天内又释放了另外 5%的肽。用 QPVP 对纳米颗粒进行涂层后，释放期和肽的量发生了明显的变化。与游离肽和未涂层纳米颗粒相比，负载抗原肽的纳米颗粒能够刺激体外巨噬细胞释放更多的一氧化氮（NO），这表明所产生的纳米颗粒系统具有免疫刺激活性。具有抗原肽延长脉冲释放的未涂层纳米颗粒可用于开发单次注射自增强疫苗制剂。通过对这些纳米颗粒进行涂层，可以改变其释放曲线和免疫原性。
