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Successful use of axonal transport for drug delivery by synthetic molecular vehicles

Aaron G. Filler¹, Garth Whiteside², Mark Bacon³, Martyn Frederickson⁴, Franklyn A. Howe⁵, Miri K. Rabinowitz⁶, Alan J. Sokoloff⁷, Terrence Deacon⁸, Chris Abell⁹, Raj Munglani¹⁰, John R. Griffiths¹¹, B. Anthony Bell¹² & Andrew Lever¹³

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1. Institute for Nerve Medicine, Department of Neurosurgery
2. Wyeth Research, Neuroscience Discovery Research
3. International Spinal Research Trust, Guildford, Surrey
4. Astex Therapeutics, Cambridge
5. St. George's Hospital Medical School, Cardiac and Vascular Sciences
6. University of Pittsburgh Medical Center, Western Psychiatric Institute & Clinic
7. Emory University, Department of Physiology
8. University of California, Berkeley, Anthropology & Neurosciences
9. University of Cambridge, Department of Chemistry
10. West Suffolk Hospital, Department of Pain Medicine and Anesthesia
11. Cancer Research UK, University of Cambridge, Cambridge Research Institute
12. St. George's Hospital Medical School, Division of Clinical Neurosciences
13. University of Cambridge, Medicine

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Document Type:

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Date:

Received 06 August 2008 15:14 UTC; Posted 07 August 2008

Subjects:

Biotechnology, Chemistry, Molecular Cell Biology, Neuroscience, Pharmacology

Tags:

• axonal transport
• drug delivery
• Pharmacology
• pain

Abstract:

We report the use of axonal transport to achieve intraneural drug delivery. We constructed a novel tripartite complex of an axonal transport facilitator conjugated to a linker molecule bearing up to a hundred reversibly attached drug molecules. The complex efficiently enters nerve terminals after intramuscular or intradermal administration and travels within axonal processes to neuron cell bodies. The tripartite agent provided 100-fold amplification of saturable neural uptake events, delivering multiple drug molecules per complex. In vivo, analgesic drug delivery to systemic and to non-targeted neural tissues was greatly reduced compared to existing routes of administration, thus exemplifying the possibility of specific nerve root targeting and effectively increasing the potency of the candidate drug gabapentin 300-fold relative to oral administration.

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This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Filler, Aaron, Whiteside, Garth, Bacon, Mark, Frederickson, Martyn, Howe, Franklyn, Rabinowitz, Miri, Sokoloff, Alan, Deacon, Terrence, Abell, Chris, Munglani, Raj, Griffiths, John, Bell, B. Anthony, and Lever, Andrew. Successful use of axonal transport for drug delivery by synthetic molecular vehicles. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.2164.1> (2008)

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