Drug targeting

The main problems currently associated with systemic drug administration ar e: even biodistribution of pharmaceuticals throughout the body; the lack of drug specific affinity toward a pathological site; the necessity of a larg e total dose of a drug to achieve high local concentration; non-specific to xicity and other adverse side-effects due to high drug doses. Drug targetin g, i.e. predominant drug accumulation in the target zone independently on t he method and route of drug administration, may resolve many of these probl ems. Currently, the principal schemes of drug targeting include direct appl ication of a drug into the affected zone, passive drug targeting (spontaneo us drug accumulation in the areas with leaky vasculature, or Enhanced Perme ability 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 acti on 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 g hosts, liposomes, and micelles have been successfully used for targeted dru g 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, poss ibility to control size and permeability of drug carrier systems and use re latively small number of vector molecules to deliver substantial quantities of a drug to the target. The practical use of the listed systems and appro aches for the delivery of therapeutic and diagnostic agents will be conside red. (C) 2000 Elsevier Science B.V. All rights reserved.