Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Kang, Y.S. et al.

Brain delivery of biotin bound to a conjugate of neutral avidin and cationized human albumin.

The delivery of pharmaceuticals through the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo, may be facilitated by conjugation of therapeutics to brain drug delivery vectors. Since cationized albumin has been shown to undergo absorptive-mediated transcytosis through the BBB in vivo, cationized human serum albumin (cHSA) is a potential brain drug delivery vector in humans. Conjugation of biotinylated therapeutics to brain drug delivery vectors is facilitated by the preparation of vector/avidin conjugates. Therefore, the present studies describe the preparation of a cHSA-avidin conjugate and the delivery of 3H-biotin bound to this conjugate through the BBB in vivo in anesthetized rats. Since the cationic nature of avidin (AV) accelerates the removal of avidin-based conjugates from blood in vivo, the present studies also describe the preparation and the pharmacokinetics of 3H-biotin bound to a conjugate of cHSA and neutral avidin (NLA). The bifunctional nature of the conjugate was retained: the cHSA/NLA conjugate contained 2.8 to 6.8 biotin binding sites per conjugate, and the BBB permeability-surface area (PS) product for 3H-biotin bound to cHSA/NLA was at least 7-fold greater than the BBB PS product for 3H-biotin bound to a conjugate of NLA and native HSA (nHSA). The systemic clearance of the cHSA conjugate was reduced 10-fold by the use of NLA as opposed to AV. The increased area under the plasma concentration curve (AUC) of the cHSA-NLA conjugate correlated with an increase in brain delivery of 3H-biotin as compared to the brain delivery achieved with the cHSA/AV conjugate.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

References

Brain delivery of biotin bound to a conjugate of neutral avidin and cationized human albumin. Kang, Y.S., Pardridge, W.M. Pharm. Res. (1994) [Pubmed]

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