School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom.
Laboratório de Bacteriologia, Instituto Butantan, São Paulo, SP, Brazil.
Int J Pharm. 2021 Apr 15;599:120407. doi: 10.1016/j.ijpharm.2021.120407. Epub 2021 Mar 3.
Polymeric nanoparticles (NPs) are recognized as potential delivery vehicles for vaccines. PLGA is a biocompatible polymer synonymous with polymeric NPs, which can be coated with other polymers such as chitosan that has intrinsic adjuvant properties as well as mucoadhesive properties. Numerous modifications and variations exist for PLGA and chitosan, which can influence the NP characteristics and the resulting immunogenicity. The current study investigated variations for making chitosan coated PLGA NPs incorporating recombinant pneumococcal surface protein A from family 2, clade 4 (PspA4Pro) antigen as a vaccine targeting the vast majority of pneumococcal strains and determine the effect of the polymers on particle size, surface charge, and surface marker upregulation on a dendritic cell (DC) line in vitro. PLGA variations tested with the ester-terminal group had the greatest detriment for prospective vaccine use, due to the lowest PspA4Pro adsorption and induction of CD40 and CD86 cell surface markers on DCs. The negatively charged chitosans exhibited the lowest surface marker expressions, similar to the uncoated NP, supporting the commonly accepted notion that positive surface charge augments immunogenic effects of the NPs. However, the study indicated that NPs made from PLGA with an acid terminated group, and chitosan HCl salt, exhibit particle characteristics, antigen adsorption efficiency and immunogenicity, which could be most suitable as a vaccine formulation.
聚合物纳米颗粒 (NPs) 被认为是疫苗的潜在递送载体。PLGA 是一种生物相容性聚合物,与聚合物 NPs 同义,它可以涂覆其他聚合物,如壳聚糖,壳聚糖具有内在的佐剂特性和黏膜黏附特性。PLGA 和壳聚糖存在许多修饰和变化,这会影响 NP 的特性和由此产生的免疫原性。本研究探讨了在制造壳聚糖涂覆的 PLGA NPs 方面的变化,该 NPs 包含来自 2 家族 4 分支的重组肺炎球菌表面蛋白 A (PspA4Pro) 抗原,作为针对绝大多数肺炎球菌菌株的疫苗,并确定聚合物对粒径、表面电荷和表面标记物上调的影响在体外树突状细胞 (DC) 系上。具有酯端基的 PLGA 变体由于对潜在疫苗使用的不利影响最大,因为对 PspA4Pro 的吸附最低,并且对 DC 上的 CD40 和 CD86 细胞表面标记物的诱导最低。带负电荷的壳聚糖表现出最低的表面标记物表达,与未涂层的 NP 相似,这支持了通常的观点,即正表面电荷增强了 NPs 的免疫原性。然而,该研究表明,由具有酸端基的 PLGA 和壳聚糖 HCl 盐制成的 NPs 表现出颗粒特性、抗原吸附效率和免疫原性,这可能是最适合作为疫苗制剂的特性。