| Summary: | PURPOSE: To design bioadhesive Gantrez AN (poly[methyl vinyl ether-co-maleic
anhydride], PVM/MA) nanoparticles (NP) coated with Vitamin B12 (Vit B12), and
investigate their application in oral antigen delivery.
METHODS: The association of Vit B12 to Gantrez AN nanoparticles was performed by
the direct attachment of reactive Vit B12 to the surface of the nanoparticles (NPB), or
linking to the copolymer chains in dimethylformamide prior to NP formation (NPBDMF).
Nanoparticles were characterized by measuring the size, zeta potential, Vit B12
association efficacy, and stability of Vit B12 on the surface of the nanoparticles. In vivo
bioadhesion study was performed by the oral administration of fluorescently-labeled
nanoparticle formulations to rats. Both systemic and mucosal immune responses were
evaluated after oral and subcutaneous immunization with ovalbumin (OVA) containing
Vit B12-coated nanoparticles.
RESULTS: The Vit B12 nanoparticles displayed homogenous size distribution with a
mean diameter of about 200 nm and a negative surface charge. The association
efficiency of Vit B12 to NPB-DMF formulation was about two times higher than to the
NPB, showing also a higher surface stability of Vit B12. The bioadhesion study
demonstrated that NPB-DMF had an important tropism to the distal portions of the gut,
which was about 2 and 3.5 times higher than the tropism observed for NPB and control
NP, respectively (P< 0.05). Oral administration of OVA-NPB-DMF induced also
stronger and more balanced serum anti-OVA titers of IgG2a (Th1) and IgG1 (Th2)
compared to control OVA-NP. In addition, oral immunization with OVA-NPB-DMF
induced a higher mucosal IgA response than subcutaneous administration.
CONCLUSIONS: These results indicate the benefits of bioadhesive Vit B12-coated
nanoparticles in oral antigen delivery eliciting systemic and mucosal immune response.
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