Targeted drug delivery system

Basic Overview of Targeted Drug Delivery Systems

1. Targeted drug delivery system Hitesh Udar M.Pharmacy PDM University Department of Pharmaceutics

2. contents Introduction Need for tdds Ideal Characteristics Advantages Disadvantages Carrier or markers Strategies of Drug targeting

3. Introduction Targeted drug delivery system is a special form of drug delivery system where the Selective and Effective Localization of drug into the target at therapeutic concentrations with limited access to non target sites takes place. It is a method of delivering medication to a patient in a m anner that inc r ea s es the concen t rat i on of t he m edi c at i on in some parts of the body relative to others. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues .

4. Goal:- To provide prolong, localized, target and protected drug interaction with the diseased tissue. To achieve a desired pharmacological response at a selected site without undesirable interaction at other sites, there by the drug have a specific action with minimum side effects & better therapeutic index. The drugs can be targeted to An organ Particular tissue or cell Intracellular sites Virus or bacterial cells

5. Need For TDDS

6. Ideal Characteristics It should be Non-toxic Biocompatible Biodegradable Physicochemical stable both in-vivo & in-vitro Restricted drug distribution to target cells or tissues or organs and should have uniform distribution. Controlled and predictable drug release. Minimal drug leakage. Carrier should be readily eliminated without causing any change in the diseased state. Preparation should be easy, reproductive and cost effective. Drug release should not effect drug action.

7. Advantages & Disadvantages Advantages Reduction of Drug side effects Reduced frequency of drug intake Reduced dose of drug Uniform blood level of drugs Maximizes the therapeutic index Avoidance of hepatic first pass metabolism Disadvantages Rapid clearance of targeted systems. Immune reactions against carrier systems. Insufficient localization of targeted systems in tumor cells. Diffusion and redistribution of released drug. Difficult to maintain stability of dosage form. High cost.

8. Carrier and Markers They are engineered vectors, which retain drug inside or onto them either via encapsulation and/ or via spacer moiety and transport or deliver it into vicinity of target cell. Carrier is one of the special molecule or system essentially required for effective transportation of loaded drug up to the pre selected sites. Pharmaceutical carriers : Polymers Microcapsules Microparticles Lipoproteins Liposomes Micelles

9. Strategies of Drug Targeting

10. Passive Targeting Drug delivery systems which are targeted to systemic circulation are characterized as Passive delivery systems. In t his te c hnique drug t a r get i ng occu r s becau s e of t he body’s natural response to physicochemical characteristics of the drug or drug carrier system. Example: uptake of some colloids by RES especially in liver or spleen => ideal substrate for passive hepatic targeting of drug

11. Inverse Targeting In this type of targeting attempts are made to avoid passive uptake of colloidal carrier by RES ( Reticulo Endothe l ial Syste m s) and hence the process is referred to as inverse targeting. T o ach i eve inve r se ta r get i ng, RES nor m al funct i on is suppressed by pre injecting large amount of blank colloidal carriers or macromolecules like dextran sulphate . This approach leads to saturation of RES and suppression of defense mechanism. This type of targeting is an effective approach to target drug(s) to non-RES organs. Example: pre-injection of large amount of blank colloidal carriers or macromolecules like dextran to saturate the RES system => drug targeting to NON-RES ORGANS

12. Active Targeting In t his app r oach ca r r i er sys tem bea r ing drug reaches to specific site on the basis of m odifica t ion m ade on i ts surface rather than natural uptake by RES. Surface modification technique include coating of surface with either a bioadhesive , nonionic sur factant or s pec i fic ce l l or tis sue ant i bodies ( i .e. monoclonal antibodies) or by albumin protein. FIRST ORDER: distribution to the capillary bed of target site like lymphatic, cerebral ventricles etc SECOND ORDER: delivery to special cells like tumor or kupffer cells in liver. THIRD ORDER: intracellular localization of dug carrier complex via endocytosis or ligand mediated entry where lysosomal degradation of carrier complex causes release of drug.

13. Ligand Mediated Targeting Achieved using specific mechanisms such as receptor dependent uptake of natural LDL particles and synthetic lipid microemulsions of partially reconstituted LDL particles coated with the apoproteins. Physical Targeting In this type of targeting some characteristics of environment changes like pH, temperature, light intensity, electric field, ionic strength small and even spec i fic st i m uli l i ke gluco s e concen t ra t i o n are used to localize the drug carrier to predetermined site. This approach was found exceptional for tumour targeting as well as cytosolic delivery of entrapped drug or genetic material.

14. Dual Targeting In t his ta r get i ng app r oach ca r r i er m ole c ule i t se lf have their own therapeutic activity and thus increase the therapeutic effect of drug. For example, a carrier molecule having its own antiviral activity can be loaded with antiviral drug and the net synergistic effect of drug conjugate was observed .

15. Double Targeting T e m poral and spat i al m ethodologi e s are co m bined to target a carrier system, then targeting may be called double targeting. Spatial placement relates to targeting drugs to specific organs, tissues, cells or even subcellular co m part m ent. Wher eas te m poral del i very re fers to controlling the rate of drug delivery to target site.

16. Combination Targeting These targeting systems are equipped with carriers, polymers and homing devices of molecular specificity that could provide a direct approach to target site. Modification of proteins and peptides with natural polymers such as polysaccharides, or synthetic polymers such as poly(ethylene glycol) may alter their physical characteristics and favour targeting the specific compartment, organs or their tissues within their vasculature. Further vectorization of these modified proteins and peptides into vesicular or microparticulate carriers may take advantage of the intrinsic and inherited properties of carrier to achieve a site specific active targeting of encapsulated contents.

17. Problems Associated with TDDS Rapid clearance of targeted systems specially antibody targeted carriers. Immune reactions against intravenous administered carrier systems. Target tissue heterogeneity. Problems of insufficient localization of targeted systems into tumour cells. Down regulation and sloughing of surface epitopes. Diffusion and redistribution of released drug leading to non-specific accumulation.

18. Thank You