Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

Aaron G Filler , Garth T Whiteside , Mark Bacon , Martyn Frederickson , Franklyn A Howe , Miri D Rabinowitz , Alan J Sokoloff , Terrence W Deacon , Chris Abell , Raj Munglani , John R Griffiths , B ANTHONY Bell and Andrew ML Lever
BMC Neuroscience 2010, 11:8doi:10.1186/1471-2202-11-8, Published: 20 January 2010

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Background

Targeted delivery of pharmaceutical agents into selected populations of CNS neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior.

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