Zhang Jing, Field Catherine J, Vine Donna, Chen Lingyun
Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, T6G 2P5, Canada.
Pharm Res. 2015 Apr;32(4):1288-303. doi: 10.1007/s11095-014-1533-x. Epub 2014 Oct 16.
Intestinal absorption of vitamin B12 (VB12) is a major challenge in combating pernicious anemia due to intrinsic factor (IF) deficiency.
The aim of this study was to explore the feasibility of using soy protein isolates (SPI) nanoparticles to improve the intestinal transport and absorption of VB12.
Three different sized VB12-loaded SPI nanoparticles were produced by modulating preparation conditions using a cold-gelation method. The intestinal uptake and transport mechanisms of SPI nanoparticles for VB12 delivery were investigated and related to particle size.
SPI nanoparticles were not cytotoxic to Caco-2 cells and were effectively internalized into the cytoplasm via multiple endocytosis pathways including clathrin- and/or caveolae-mediated endocytosis and macropinocytosis routes. VB12 transport across the Caco-2 cell monolayers was increased to 2-3 times after nanoencapsulation, which was dependent on particle size, in the increasing order of 30 > 100 > 180 nm. Using inhibitor block method, the transport of 30 and 100 nm SPI nanoparticles appeared to be clathrin-mediated transcytosis and macropinocytosis routes. The intestinal transport of VB12, assessed using rodent jejunum in Ussing chambers, was improved up to 4-fold after being encapsulated into 30 nm SPI nanoparticles.
The findings suggest that SPI nanoparticles could be a promising carrier to facilitate the oral delivery of VB12.
由于内因子(IF)缺乏,维生素B12(VB12)的肠道吸收是治疗恶性贫血的一项重大挑战。
本研究旨在探讨使用大豆分离蛋白(SPI)纳米颗粒改善VB12肠道转运和吸收的可行性。
采用冷凝胶法调节制备条件,制备了三种不同尺寸负载VB12的SPI纳米颗粒。研究了SPI纳米颗粒用于VB12递送的肠道摄取和转运机制,并与粒径相关。
SPI纳米颗粒对Caco-2细胞无细胞毒性,并通过包括网格蛋白和/或小窝介导的内吞作用以及巨胞饮作用途径在内的多种内吞途径有效地内化到细胞质中。纳米包封后,VB12跨Caco-2细胞单层的转运增加到2至3倍,这取决于粒径,粒径大小顺序为30>100>180nm。使用抑制剂阻断法,30和100nm SPI纳米颗粒的转运似乎是网格蛋白介导的转胞吞作用和巨胞饮作用途径。在Ussing室中使用啮齿动物空肠评估,VB12被包裹在30nm SPI纳米颗粒中后,其肠道转运提高了4倍。
研究结果表明,SPI纳米颗粒可能是促进VB12口服递送的一种有前景的载体。