Drug targeting sd

drug targeting

1. DRUG TARGETING Presented by Grandhi Sandeep Ganesh 1

2. ABSTRACT Targeted drug delivery also known as smart drug delivery ,is a method of treatment that involves the selective transport of drugs to targeted organs, tissues and cells through a variety of drugs carrier . It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to over come problems such as limited solubility , drug aggregation , lack of selectivity and to reduce normal tissue damage. The various drug targeting strategies are- Active targeting , passive targeting , inverse targeting , physical targeting , ligand mediated targeting , dual targeting and double targeting , combinational targeting. 2

3. DEFINITION It is defined as the ability of a drug to accumulate the target organ or tissue selectively such that the concentration of drug at diseased site is high (target organ)and the concentration is low at non-target organ to prevent unwanted side effects or toxic effects. CARRIER carriers are molecules or any other systems responsible for the successful transportation of the drug to the site of interest. 3

4. 4 CARRIER SYSTEMS USED ARE: 1.colloidal carriers 2.cellular carriers 3.supramolecular delivery systems 4.polymer based system 5.macromolecular carriers

5. Pharmaceutical reason: Drug instability Low solubility Pharmacokinetic reasons : Poor absorption Short half –life Large volume of distribution Pharmacodynamic reasons: Low specificity Low therapeutic index 5 REASON FOR DRUG TARGETING

6. LEVELS OF DRUG TARGETING 6

7. It involves the modification or functionalization of drug carriers so that the contents are delivered to the site. TYPES: 1.First order targeting 2.Second order targeting 3.Third order targeting 1.FIRST ORDER TARGETTING:(ORGAN COMPARTMENTALIZATION) Restricted distribution of the drug carrier system to the capillary bed of a pre determined target site,organ or tissue. Eg:compartmental targeting in lymphatics,peritoneal cavity,joints,lungs,eyes etc. 7 ACTIVE TARGETING

8. 2.SECOND ORDER TARGETING:( CELLULAR TARGETING) The selective drug delivery to a specific cell type such as tumour cells. Eg : Selective drug delivery to kupffer cells in the liver. 3.THIRD ORDER KINETICS:(INTRACELLULAR TARGETING) Drug delivery specifically to the intracellular organelles of the target cells. Eg : Receptor based ligand mediated endocytosis Lysosomal degradation of liver 8

9. PASSIVE TARGETING System that target the systemic circulation are generally characterised as passive drug delivery system. Passive targeting involves transport of nano carriers through leaky tumor capillary fenestrations into the tumor interstitium and cells by passive diffusion. Drug targeting occurs due to body’s natural response to the physico chemical properties of drug or carriers. Bio distribution of carrier system through which it eventually accumulate in organ compartment of body. Eg : uptake of some colloids by RES especially in liver or spleen . 9

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11. INVERSE TARGETING It is a result of the avoidance of passive uptake of colloidal carriers by the RES. It is based on attempts to circumvent and avoid passive uptake of colloidal carriers by RES leading to reversion of bio-distribution trend of the carrier. Other strategies include modification and defined manipulation of the size , surface charge , composition , surface rigidity and hydro- philicity characteristics of carriers for desirable bio-fate. It can be achieved by: Suppressing the function of RES by pre injection of a large amount of blank colloidal carriers or macromolecules like dextran sulphate . 11

12. LIGAND MEDIATED TARGETING Ligands are carrier surface group and which can selectively direct the carrier to the pre-specified site housing the appropriate receptor units to serve as “homing device” to the carrier/drug. most of the carrier are colloidal in nature and can be specifically funtionalized using various biologically relevant molecular ligands including polypeptides,oligosaccharides , viral proteins and fusogenic residues It can be achieved using specific mechanisms such as receptor dependent uptake of natural LDL particles and synthetic lipid micro emulsions of partially reconstituted LDL particles coated with the apoproteins . 12

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14. PHYSICAL TARGETING DEFINITION: It is defined as selective drug delivery that is programmed or monitored using at external level(ex-vivo) with the help of physical means like pH , temperature , light intensity & ionic strength. It is also known as triggered release. This approach was found exceptional for tumor targeting as well as cytosolic delivery of entrapped drug or genetic material 14

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16. 16 Drug targeting using carrier molecules, having intrinsic antiviral effect thus synergies the antivira leffect of the loaded active drug. Based on this approach, drug conjugates can be prepared with fortified activity profile against the viral replication. In this targeting approach, carrier molecule, itself have their own therapeutic activity and thus increase the therapeutic effect of drug. Advantages: The virus replication process can be attacked at multiple points, excluding the possibilities of resistant viral strain development. DUAL TARGETING

17. 17 In order to achieve a double targeting effect, site specificity of the drug, by virtue of targeting moiety, a high specificity module(mainly a photosensitizer ) is linked to antibodies Double Targeting Targeting drugs to specific organs, tissues, cells or even sub cellular compartment Spatial control Temporal control Double targeting Controlling the rate of drug delivery to target site

18. 18 Suggested by Petit and Gombtz . Site-specific delivery of proteins and peptides. These targeting systems are equipped with carriers, polymers and homing devices of molecular specificity that could provide a direct approach to target site COMBINATION TARGETING

19. REFERENCES Lachman / Liberman’s The Theory and Practice of Industrial pharmacy . Targeted and controlled drug delivery (Novel carrier systems),S P Vyas and R K Khar . www.sciencedirect.com 19