BACKGROUND: Intestinal absorption of vitamin B12 (VB12) is a major challenge in combating pernicious anemia due to intrinsic factor (IF) deficiency. PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: The findings suggest that SPI nanoparticles could be a promising carrier to facilitate the oral delivery of VB12.
BACKGROUND: Intestinal absorption of vitamin B12 (VB12) is a major challenge in combating pernicious anemia due to intrinsic factor (IF) deficiency. PURPOSE: 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. METHODS: 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. RESULTS: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. CONCLUSIONS: The findings suggest that SPI nanoparticles could be a promising carrier to facilitate the oral delivery of VB12.
Authors: Eva C Arrua; Olga Hartwig; Duy-Khiet Ho; Brigitta Loretz; Xabier Murgia; Claudio J Salomon; Claus-Michael Lehr Journal: Pharm Res Date: 2021-05-17 Impact factor: 4.200