Intestinal Uptake and Transport of Vitamin B12-loaded Soy Protein Nanoparticles

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Abstract
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.

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