Soy Protein Nanoparticles as an Oral Delivery Vehicle for Nutraceuticals

• Author / Creator

  Jing, Zhang

• The objective of this research was to explore the feasibility of using SPI nanoparticles to improve the absorption of vitamin B12 (VB12) using in-vitro and ex-vivo models. The molecular interactions between soy proteins and VB12 were firstly studied and the results revealed that VB12 was bound to the interior of three-dimensional protein network mainly via hydrophobic interactions to form soy proteins-VB12 complexes. VB12-loaded SPI nanoparticles with different particle size (30, 100 and 180 nm) and surface charge (-17, 22 and -40 mV) were obtained using a cold-gelation method by adjusting preparation conditions and applying surface coating with chitosan and sodium alginate. SPI nanoparticles exhibited uniform size distribution and spherical shape. SPI nanoencapsulation led to a slower VB12 release in simulated gastric and intestinal fluids. Surface coating retarded the release of VB12 from SPI nanoparticles. All the nanoparticles showed a low cytotoxicity and high cellular uptake efficiency in Caco-2 cells. Cellular uptake of nanoparticles was dependent on energy, particle concentration and incubation temperature, suggesting the active endocytosis pathways. The transport efficiency of VB12 across Caco-2 cell monolayers was significantly increased after nanoencapsulation, up to 3 times. 30 nm SPI nanoparticles demonstrated the highest VB12 transport efficiency compared with larger-sized and surface modified ones. The transcytosis of SPI nanoparticles (30-180 nm) was predominantly via clathrin-mediated and macropinocytosis pathways. In addition, the caveolae-mediated transcytosis pathway was partially involved in the transport of 30 nm SPI nanoparticles. The transcytosis of chitosan modified SPI particles was involved in the clathrin-/caveolae-independent pathway, while that of alginate/chitosan modified nanoparticles was through the clathrin-/caveolae-mediated and macropinocytosis pathways. In addition to the transcellular pathways, all the nanoparticles could facilitate the paracellular transport of VB12 via tight junctions. Since 30 nm SPI nanoparticles showed the optimized VB12 transport efficiency, which were further applied on the ex vivo Ussing chamber test. The results indicated that 30 nm SPI nanoparticles enhanced the intestinal absorption of VB12, up to 4 times. The findings in this study suggested that SPI nanoparticles could be a promising oral carrier for VB12, which is recommended for further study via in vivo tests in the future.

• Subjects / Keywords

  • Vitamin B12
  • Paracellular pathway
  • Nanoparticles
  • Soy protein isolate
  • Transcellular pathway
  • Surface charge
  • Particle size

• Graduation date

  Fall 2014

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3K35MN6X

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.