DRUG TARGETING

Prathap.N

Definition
Targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others.

Mechanism
The external stimulus (i.e., chemical substance) physically binds to the biological target. The interaction between the substance and the target may be: noncovalent reversible covalent irreversible covalent Depending on the nature of the stimulus, the following can occur: There is no direct change in the biological target, except that the binding of the substance prevents other endogenous substances such as activating hormone to bind to the target. Depending on the nature of the target, this effect is referred as receptor antagonism, enzyme inhibition, or ion channel blockade. A conformational change in the target is induced by the stimulus which results in a change in target function. This change in function can mimic the effect of the endogenous.

Drug targets
The term drug target is frequently used in pharmaceutical research to describe the native protein in the body whose activity is modified by a drug resulting in a desirable therapeutic effect. common drug targets include: G protein-coupled receptors enzymes ion channels -ligand-gated ion channels -voltage-gated ion channels nuclear hormone receptors structural proteins membrane transport proteins

Applications of drug targeting

delivery of toxic drugs to tumors delivery of DNA vectors to target cell type for genetic corrections targeting to vasculature (The arrangement of blood vessels in the body) targeting to pathogen-infected cells crossing blood-brain barrier3

Targeting approaches
receptor-ligand-based targeting guide drug to target based on unique or overexpressed receptor on target cell type antibody targeting Pros: high affinity high specificity cons: need to be humanized to avoid rapid opsonization need to consider possible Fc receptor binding (Fc = fragment crystallizable)

targeting to vasculature
Inflammatory signals delivered from peripheral tissues to endothelial cells induce up regulation of threat signals on the surface of these cells within the lumen of blood vessels
Cytokine signals such as IL-1, TNF

Chronic inflammation: up regulation of E-selectin Acute inflammation: up regulation of P-selectin Used to direct neutrophils and monocytes to sites of inflammation

Reverse targeting
attraction of target cells to carrier

Issues in Drug Targeting

collateral damage Tumor and viral escape Immunological response to targeting agent

Integrating targeting, activation, and intracellular delivery

intracellular delivery of a cellular toxin to tumors .Target receptor also triggers receptormediated endocytosis targeted delivery to cytosol by functionalized pH-sensitive liposomal carriers