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Brain Uptake Of Thiamine-coated Nanoparticles.

P. Lockman, M. Oyewumi, J. Koziara, K. Roder, R. Mumper, D. Allen
Published 2003 · Chemistry, Medicine

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Recently, a novel nanoparticle (NP) comprised of emulsifying wax and Brij 78 was shown to have significant brain uptake using the in-situ rat brain perfusion technique. To further these studies and to specifically target brain, we have incorporated thiamine as a surface ligand on the nanoparticles. Solid nanoparticles were prepared from oil-in-water microemulsion precursors. Nanoparticles were radiolabeled and a thiamine ligand (thiamine linked to distearoylphosphatidylethanolamine via a polyethylene glycol spacer) was coated on the surface of the nanoparticles. Initial experiments focused on assessing uptake of [3H]nanoparticles with and without thiamine surface ligands. Biodistribution nanoparticle studies were also carried out in BALB/c mice. The results showed: (1) the effectiveness of using microemulsions as precursors to engineer nanoparticles, (2) kinetic modeling for brain uptake of nanoparticles with and without the thiamine surface ligands, and (3) initial data suggesting mechanisms for nanoparticle brain entry. Comparison of NP brain uptake demonstrated that the thiamine-coated nanoparticle associated with the blood-brain barrier (BBB) thiamine transporter and had an increased K(in) between 45 and 120 s (thiamine coated NP 9.8 +/- 1.1 x 10(-3) ml/s/g versus uncoated NPs; 7.0 +/- 0.3 x 10(-3) ml/s/g). It was concluded that the thiamine ligand facilitated binding and/or association with blood-brain barrier thiamine transporters, which may be a viable mechanism for nanoparticle mediated brain drug delivery.
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