Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand.
Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand.
AAPS PharmSciTech. 2020 May 15;21(4):134. doi: 10.1208/s12249-020-01689-x.
This work described the development of a cationic polylactic acid (PLA)-based nanoparticles (NPs) as an antigen delivery system using dimethyldioctadecylammonium bromide (DDA) to facilitate the engulfment of BSA-FITC by porcine alveolar macrophages (3D4/2 cells) and heat-labile enterotoxin subunit B (LTB) to enhance the transport of BSA-FITC across M cells. The experimental design methodology was employed to study the influence of PLA, polyvinyl alcohol (PVA), DDA, and LTB on the physical properties of the PLA-based NPs. The size of selected cationic PLA NPs comprising 5% PLA, 5% PVA, and 0.6% DDA with or without LTB absorption was range from 367 to 390 nm with a polydispersity index of 0.26, a zeta potential of + 26.00 to + 30.55 mV, and entrapment efficiency of 41.43%. Electron micrographs revealed NPs with spherical shape. The release kinetic of BSA from the NPs followed the Korsmeyer-Peppas kinetics. The cationic PLA NPs with LTB surface absorption showed 3-fold increase in BSA-FITC transported across M cells compared with the NPs without LTB absorption. The uptake studies demonstrated 2-fold increase in BSA-FITC intensity in 3D4/2 cells with cationic NPs as compared with anionic NPs. Overall, the results suggested that LTB decreased the retention time of BSA-FITC loaded in the cationic PLA NPs within the M cells, thus promoting the transport of BSA-FITC across the M cells, and cationic NPs composed of DDA help facilitate the uptake of BSA-FITC in the 3D4/2 cells. Further studies in pigs with respiratory antigens will provide information on the efficacy of cationic PLA NPs as a nasal antigen carrier system.
本工作描述了一种基于阳离子聚乳酸（PLA）的纳米粒子（NPs）的开发，该纳米粒子使用二甲基二十八烷基溴化铵（DDA）促进牛肺泡巨噬细胞（3D4/2 细胞）吞噬 BSA-FITC，并使用不耐热肠毒素亚单位 B（LTB）增强 BSA-FITC 通过 M 细胞的转运。实验设计方法用于研究 PLA、聚乙烯醇（PVA）、DDA 和 LTB 对基于 PLA 的 NPs 物理性质的影响。选择的阳离子 PLA NPs 的大小包括 5% PLA、5% PVA 和 0.6% DDA，有或没有 LTB 吸收，粒径范围为 367 至 390nm，多分散指数为 0.26，zeta 电位为+26.00 至+30.55mV，包封效率为 41.43%。电子显微镜照片显示 NPs 呈球形。BSA 从 NPs 中的释放动力学遵循 Korsmeyer-Peppas 动力学。与没有 LTB 吸收的 NPs 相比，带有 LTB 表面吸收的阳离子 PLA NPs 使穿过 M 细胞的 BSA-FITC 转运增加了 3 倍。摄取研究表明，与阴离子 NPs 相比，阳离子 NPs 使 3D4/2 细胞中 BSA-FITC 的强度增加了 2 倍。总体而言，结果表明 LTB 缩短了阳离子 PLA NPs 中 BSA-FITC 的保留时间，从而促进了 BSA-FITC 通过 M 细胞的转运，并且由 DDA 组成的阳离子 NPs 有助于促进 3D4/2 细胞中 BSA-FITC 的摄取。在具有呼吸道抗原的猪中进一步研究将提供关于阳离子 PLA NPs 作为鼻腔抗原载体系统的功效的信息。
