Combined use of carboxyl-directed protein pegylation and vector-mediated blood-brain barrier drug delivery system optimizes brain uptake of brain-derived neurotrophic factor following intravenous administration.

Purpose: Peptide drug delivery to the brain requires optimization of (a) plasma pharmacokinetics and (b) blood-brain barrier (BBB) permeability. In the present studies, plasma pharmacokinetics are improved with protein pegylation and BBB transport is facilitated with the use of vector-mediated drug delivery using the OX26 monoclonal antibody (MAb) to the rat transferrin receptor, which undergoes receptormediated transcytosis through the BBB in vivo.

Methods: A conjugate of OX26 and streptavidin (SA), designated OX26/SA, was prepared in parallel with the carboxyl-directed pegylation of brain-derived neurotrophic factor (BDNF).