Akhter Kazi Farida, Mumin Md Abdul, Lui Edmund M K, Charpentier Paul A
ACS Biomater Sci Eng. 2019 Jun 10;5(6):2916-2925. doi: 10.1021/acsbiomaterials.9b00348. Epub 2019 May 15.
Plant polysaccharides (PS) such as American ginseng polysaccharide (GPS) have drawn immense interest in the field of immunoengineering, as they offer a way to actively control immune cell behavior and stimulation. These pharmacological activities have been limited by PS's inherent physicochemical properties including large molecular size, heterogeneity, and poor solubility. In this work, we hypothesized that by nanosizing and encapsulating GPSs, we could enhance their immunomodulation by increased penetration and absorption through the GI tract. Herein, GPS nanoparticles (NPs) of average size 20 nm (± 4 nm) were prepared using a microfluidic approach, then encapsulated within porous nanospheres (diameter 180 ± 10 nm) of biodegradable gelatin to enhance their oral delivery. To locate the GPS NPs inside the gelatin, we encapsulated fluorescent-labeled GPS in gelatin and analyzed using confocal microscopy. An investigation on tumor induced macrophage cell lines showed a concentration dependent enhanced immunostimulation with the encapsulated GPS NPs. The immunomodulation was then studied for different formulations of GPS through oral gavage in Swiss albino mice. The results showed that the production of proinflammatory mediators in blood samples was significantly increased for the encapsulated GPS in a dose- and time-dependent manner compared to other GPS treatments. This study shows that GPS and potentially other PS systems' immunomodulation properties can be significantly enhanced for use in simple oral drug delivery.
植物多糖(PS),如西洋参多糖(GPS),在免疫工程领域引起了极大的关注,因为它们提供了一种主动控制免疫细胞行为和刺激的方法。这些药理活性受到PS固有物理化学性质的限制,包括大分子尺寸、异质性和低溶解性。在这项工作中,我们假设通过将GPS纳米化和封装,可以通过增加其在胃肠道中的渗透和吸收来增强其免疫调节作用。在此,我们采用微流控方法制备了平均尺寸为20 nm(±4 nm)的GPS纳米颗粒(NPs),然后将其封装在可生物降解明胶的多孔纳米球(直径180±10 nm)中,以增强其口服给药效果。为了确定GPS NPs在明胶中的位置,我们将荧光标记的GPS封装在明胶中,并使用共聚焦显微镜进行分析。对肿瘤诱导的巨噬细胞系的研究表明,封装的GPS NPs具有浓度依赖性的增强免疫刺激作用。然后,通过对瑞士白化小鼠进行灌胃,研究了不同配方的GPS的免疫调节作用。结果表明,与其他GPS处理相比,封装的GPS在血液样本中促炎介质的产生呈剂量和时间依赖性显著增加。这项研究表明,GPS以及潜在的其他PS系统的免疫调节特性可以显著增强,以用于简单的口服药物递送。