Drug targeting

The main problems currently associated with systemic drug administration are: even biodistribution of pharmaceuticals throughout the body; the lack of drug specific affinity toward a pathological site; the necessity of a large total dose of a drug to achieve high local concentration; non-specific toxicity and other adverse side-effects due to high drug doses. Drug targeting, i.e. predominant drug accumulation in the target zone independently on the method and route of drug administration, may resolve many of these problems. Currently, the principal schemes of drug targeting include direct application of a drug into the affected zone, passive drug targeting (spontaneous drug accumulation in the areas with leaky vasculature, or Enhanced Permeability and Retention-EPR-effect), 'physical' targeting (based on abnormal pH value and/or temperature in the pathological zone), magnetic targeting (or targeting of a drug immobilized on paramagnetic materials under the action of an external magnetic field), and targeting using a specific 'vector' molecules (ligands having an increased affinity toward the area of interest). The last approach provides the widest opportunities. Such pharmaceutical carriers as soluble polymers, microcapsules, microparticles, cells, cell ghosts, liposomes, and micelles have been successfully used for targeted drug delivery in vivo. Though the direct conjugation of a drug molecule with a targeted moiety is also possible (immunotoxin), the use of microreservoir-type systems provides clear advantages, such as high loading capacity, possibility to control size and permeability of drug carrier systems and use relatively small number of vector molecules to deliver substantial quantities of a drug to the target. The practical use of the listed systems and approaches for the delivery of therapeutic and diagnostic agents will be considered. (C) 2000 Elsevier Science B.V. All rights reserved.