A model of axonal transport drug delivery

Abstract

In this paper a model of targeted drug delivery by means of active (motor-driven) axonal transport is developed. The model is motivated by recent experimental research by Filler et al. (A. G. Filler, G. T. Whiteside, M. Bacon, M. Frederickson, F. A. Howe, M. D. Rabinowitz, A. J. Sokoloff, T. W. Deacon, C. Abell, R. Munglani, J. R. Griffiths, B. A. Bell, A. M. L. Lever, Tri-partite complex for axonal transport drug delivery achieves pharmacological effect, Bmc Neuroscience 11 (2010) 8) that reported synthesis and pharmacological efficiency tests of a tri-partite complex designed for axonal transport drug delivery. The developed model accounts for two populations of pharmaceutical agent complexes (PACs): PACs that are transported retrogradely by dynein motors and PACs that are accumulated in the axon at the Nodes of Ranvier. The transitions between these two populations of PACs are described by first-order reactions. An analytical solution of the coupled system of transient equations describing conservations of these two populations of PACs is obtained by using Laplace transform. Numerical results for various combinations of parameter values are presented and their physical significance is discussed. © 2012 © Versita Warsaw and Springer-Verlag Wien.