Convection-enhanced drug delivery

Ferguson, S. Lesniak, M. S. Convection enhanced drug delivery of novel therapeutic agents to malignant brain tumors. Curr. Drug Deliv. 2007, 4, 169-180. 

The development of the first transdermal patches in the 1980s generated considerable interest in this route of drug administration. Soon afterwards, iontophoresis was rediscovered and its potential to contribute to the new field of transdermal drug delivery was examined. This work provided the basic principles for modern iontophoretic devices [13,18-21]. Furthermore, and importantly, they demonstrated the existence of a (primarily) electroosmotic, convective solvent flux during transdermal iontophoresis [10,11,22-24], and it was shown that the permselective properties of the skin (a) could be exploited to enhance the transport of neutral, polar species and (b) have a clear impact on ionic transport. Subsequent research has better characterized skin permselectivity and the factors which determine the magnitude of electroosmosis [25-27],... 

Bankiewicz, K.S., Eberling, J.L., Kohutnicka, M., et al Convection-enhanced delivery of AAV vector in parkinsonian monkeys in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. Exp. Neurol. 164, 2-14 (2000). doi 10.1006/exnr.2000.7408... 

Diffusion, particularly of macromolecules, plays a minor role in transport across this barrier. Convection due to leaky blood vessels, on the other hand, should enhance delivery yet the movement of drugs and macromolecnles into the interstitinm is often surprisingly limited. This is generally attributed to a diminished hydrostatic pressure gradient between the vascular compartment and the interstitium, which is explained by decreased vascnlar pressure or increased interstitial pressure, or both. 

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