Alqahtani Mohammed S, Syed Rabbani, Alshehri Meshal
Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Nanomedicine & Biotechnology Research Unit, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Polymers (Basel). 2020 Nov 2;12(11):2576. doi: 10.3390/polym12112576.
The main objective of the present study was to investigate the hemo and immune compatibility of gliadin nanoparticles as a function of particle size. Gliadin nanoparticles of different size were prepared using a modified antisolvent nanoprecipitation method. The hemolytic potential of gliadin nanoparticles was evaluated using in vitro hemolysis assay. Phagocytic uptake of gliadin nanoparticles was studied using rat polymorphonuclear (PMN) leukocytes and murine alveolar peritoneal macrophage (J774) cells. In vivo immunogenicity of gliadin nanoparticles was studied following subcutaneous administration in mice. Gliadin nanoparticles were non-hemolytic irrespective of particle size and hence compatible with blood components. In comparison to positive control zymosan, gliadin nanoparticles with a size greater than 406 ± 11 nm showed higher phagocytic uptake in PMN cells, while the uptake was minimal with smaller nanoparticles (127 ± 8 nm). Similar uptake of gliadin nanoparticles was observed in murine alveolar peritoneal macrophages. Anti-gliadin IgG antibody titers subsequent to primary and secondary immunization of gliadin nanoparticles in mice were in the increasing order of 406 ± 11 nm < 848 ± 20 nm < coarse suspension). On the other hand, gliadin nanoparticles of 127 ± 8 nm in size did not elicit immunogenic response. Phagocytosis and immunogenicity of gliadin nanoparticles are strongly influenced by particle size. The results of this study can provide useful information for rational design of protein-based nanomaterials in drug delivery applications.
本研究的主要目的是研究麦醇溶蛋白纳米颗粒的血液和免疫相容性与粒径的关系。采用改良的反溶剂纳米沉淀法制备了不同粒径的麦醇溶蛋白纳米颗粒。采用体外溶血试验评估麦醇溶蛋白纳米颗粒的溶血潜力。利用大鼠多形核(PMN)白细胞和小鼠肺泡巨噬细胞(J774)研究了麦醇溶蛋白纳米颗粒的吞噬摄取情况。在小鼠皮下给药后研究了麦醇溶蛋白纳米颗粒的体内免疫原性。无论粒径大小,麦醇溶蛋白纳米颗粒均无溶血作用,因此与血液成分相容。与阳性对照酵母聚糖相比,粒径大于406±11 nm的麦醇溶蛋白纳米颗粒在PMN细胞中的吞噬摄取更高,而较小的纳米颗粒(127±8 nm)的摄取量最小。在小鼠肺泡巨噬细胞中也观察到了类似的麦醇溶蛋白纳米颗粒摄取情况。小鼠初次和二次免疫麦醇溶蛋白纳米颗粒后,抗麦醇溶蛋白IgG抗体滴度按406±11 nm < 848±20 nm < 粗悬液的顺序增加。另一方面,粒径为127±8 nm的麦醇溶蛋白纳米颗粒未引发免疫原性反应。麦醇溶蛋白纳米颗粒的吞噬作用和免疫原性受粒径的强烈影响。本研究结果可为基于蛋白质的纳米材料在药物递送应用中的合理设计提供有用信息。