DRUG TARGETING: BASIC CONCEPTS AND DRUG CARRIER SYSTEMS- A REVIEW
Dadhichi College of Pharmacy, BPUT, Orissa
The aim of this reviewis to introduce the basic principles of drug targeting as they have evolved over previous decades. The most important chemical features and biological behavioural characteristics of the carrier molecules exploited for drug targeting purposes will be addressed. Furthermore, a selection of drug targeting preparations that are either in the stage of clinical testing or have been approved for application in the clinic is discussed. As the basis of drug development lies in the understanding of the molecular basis of diseases, selective interference with regulatory processes in health and disease by drug targeting will become a powerful technology. Drug targeting can, in this respect, serve both as a therapeutic approach and as a research tool in unravelling the functions of these processes in normal physiology and under patho-physiological conditions.
Reference Id: PHARMATUTOR-ART-1505
Target drug delivery system is a special form of drug delivery system where the pharmacologically active agent or medicament is selectively targeted or delivered only to its site of action or absorption and not to the non-target organs or tissues or cells. Targeted drug delivery implies for selective and effective localization of pharmacologically active moiety at pre identified (preselected) target in therapeutic concentration, while restricting its access to non-target normal cellular linings, thus minimizing toxic effects and maximizing therapeutic index. Targeting of drugs to special cells and tissues of the body without their becoming a part of systemic circulation is a very novel idea. If a drug can be administered in a form such that it reaches the receptor sites in sufficient concentration without disturbing in extraneous tissue cells.
Such products are prepared by considering-
Specific properties of target cells.
Nature of markers or transport carriers or vehicles, which convey drug to specific receptors.
Ligands and physically modulated components.
Advantages of drug targeting:
• Drug administration protocols may be simplified;
• Drug quantity may be greatly reduced as well as the cost of therapy;
• Drug concentration in the required sites can be sharply increased without negative effects on non-target compartments.
Disadvantages of drug targeting:
• Rapid clearance of targeted systems.
• Immune reactions against intravenous administered carrier systems.
• Insufficient localization of targeted systems into tumour cells.
• Diffusion and redistribution of released drugs.
Ideal characteristics of targeted drug delivery system:
• Targeted drug delivery system should be- biochemically inert (non-toxic), non-immunogenic.
• Both physically and chemically stable in vivo and in vitro.
• Restrict drug distribution to target cells or tissues or organs and should have uniform capillary distribution.
• Controllable and predictable rate of drug release.
• Drug release should not affect thedrug action.
• Therapeutic amount of drug release.
• Minimal drug leakage during transit.
• Carriers used must be bio-degradable or readily eliminated from the body without any problem.
• The preparation of the delivery systemshould be easy or reasonably simple, reproductive and cost effective.
TYPES OF DRUG TARGETING:
An ideal targeted drug delivery approach would not only increase therapeutic efficacy of drugs but also decrease the toxicity associated with drug to allow lower doses of the drug to be used in therapy. Two approaches are used passive targeting and active targeting.
1. Passive targeting: Passive targeting refers to the accumulation of drug or drug-carrier system at a particular site due to physicochemical or pharmacological factors. Drug or drug carrier nanosystems can be passively targeted making use of the patho-physiological and anatomical opportunities.eg include targeting of anti-malarial drugs for treatment of leishmiansis, brucellosis, candiadsis
2. Active targeting : Active targeting employs specific modification of a drug/drug carrier nano systems with active? agents having selective affinity for recognizing and interacting with a specific cell, tissue or organ in the body . Direct coupling of drugs to targeting ligand, restricts the coupling capacity to a few drug molecules. In contrast, coupling of drug carrier nanosystems to ligands allows import of thousands of drug molecules by means of one receptor targeted ligand. Example of active targeting is use of monoclonal antibody the treatment of cancer.
This active targeting approach can be furth further classified into three different levels of targeting.
1. First order targeting it refers to restricted distribution of the drug carrier systems to the capillary bed of a predetermined target site, organ or tissue. Example includes compartmental targeting in lymphatics, peritoneal cavity, plural cavity, cerebral ventricles, eyes, joints, etc.
2. Second order targeting selective delivery of drugs to specific cell types such as tumour cells and not to the normal cells is referred as second order targeting .Eg include selective drug delivery to kupffer cells in the liver.
3. Third order targeting defined as drug delivery specifically to the intracellular site of targeted cells.eg include receptor based ligand mediated entry of a drug complex into a cell by endocytosis.
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