Targeted Drug Delivery Systems

Introduction

• Targeted drug delivery systems have been designed on the concept of magic bullets given by Dr. Paul Ehrlich.

• The concept is associated with the development of such systems which when in the body, direct the drug only to its site of action.

• Thereby providing maximum therapeutic response with less toxic effects due to decreased distribution of drug to other body tissues.

• Targeted drug delivery systems are those in which maximum drug concentration is achieved at the specific site of drug action either by using inert forms of active drug (or) buy utilizing specially designed polymers.

• Targeted drug delivery systems which employs a biologically insert polymer as a carrier to carry the drug to its site of action are referred as  drug-carrier delivery systems.

• In these, the drug can be either entrapped within the carrier (or) covalently bonded to it.

• Several promising drug-carrier systems have been developed, which utilize nanoparticles, liposomes, RBCs etc… as carrier molecules.

Ideal Properties of Drug-Carrier Delivery Systems

 The drug-carrier delivery systems should possess the following characteristics,

• They should enhance the drug action by prolonging its systemic circulation.

• They should increase  drug concentration at its site of action.

• They should decreased (or) prevent tissue toxicity.

• They should prevent the drug from undergoing metabolic degradation.

• They should carry the drug during the transit and release it only at the site of action at an appropriate rate.

Mechanisms of Drug-Carrier Delivery Systems

The choice of a suitable mechanism for a Drug-Carrier delivery system depends on the drug, the requirements and the diseased condition.

1. Passive Targeting

• This mechanism utilizes normal passive uptake of the carrier by certain body tissues and their subsequent accumulation.

• Such carrier can be used to direct the drugs to those organs which show high affinity towards them.

Example :  Certain colloids are selectively taken up by reticloendothelial system (RES) especially of liver and spleen. Therefore, such colloids can be used as carrier for drugs acting on liver and spleen.

2. Active Targeting

• This mechanism uses ligands or engineered homing devices, which facilitate the binding of drug-carrier to the target cells and therefore helps in site-specific drug delivery.

• Active targeting is of the following two types.

(a) Ligand-Mediated Targeting

• In this, certain physiological ligands such as polypeptides, oligosaccharides, antibodies, viral proteins etc., are used for functionalizing the carriers.

• Such modified carriers are then able to transfer the drug to its site of action.

(b) Physical Targeting

• In this external conditions of the bio-environment such as temperature, pH etc., are monitored to ensure site-specific drug delivery.

Example: The delivery of liposomes and microspheres to a pre-selected capillary bed can be brought about by external application of magnetic field.

3. Inverse Targeting

• It is the opposite of passive targeting i.e., it prevents the uptake of carriers by certain body tissues, especially by the RES.

• Inverse targeting can be achieved by the following approaches.

a. In this approach, initially large volumes of colloidal carriers, macromolecules (dextran sulphate) or blank carriers (without any drug) are parenterally administered.

 These substances help in blocking the RES and hence impair the immune system. Later when actual carrier-drug delivery system is administered, it is not taken up by the RES and hence is directed exclusively to the site of action.

b. Modifying certain characteristics of carriers such as size, hydrophilicity, composition, surface charge etc.

4. Double Targeting

• Double targeting involves a combination of two approaches, one which deals with active or passive targeting of drugs and another which is concerned with the drug release pattern desired.

Merits of Targeted Drug Delivery Systems

• These systems decrease the amount of drug required for administration, which is beneficial for drugs with low therapeutic index.

• Maximum amount of the drug administered reaches the site of action, therefore only minor quantities reach the other body tissues.

• Enable the drug to elicit maximum therapeutic activity.

• Prevent the degradation or inactivation of drug during its transport to the site of action. 

• Preventany adverse reactions due to drug-induced toxicity