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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Filler, A., Whiteside, G., Bacon, M. et al. Successful use of axonal transport for drug delivery by synthetic molecular vehicles. Nat Prec (2008). https://doi.org/10.1038/npre.2008.2164.1
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DOI: https://doi.org/10.1038/npre.2008.2164.1