INTRODUCTION TO DRUG TARGETTING PPT- S Panda.pptx

Introduction and various levels of drug targetting

1. by Dr. Satyajit Panda Asst. Prof. INSTITUTE OF PHARMACY & TECHNOLOGY, SALIPUR DRUG TARGETTING

2. CONTENTS Introduction History Carriers types Levels of Drug targeting Problems associated with Drug targeting Advanced Carriers for Drug targeting Conclusion

3. Drug targeting systems are used to achieve site- specific drug delivery TARGETED DRUG DELIVERY Tumour Tumour Conventional formulation Targeted drug delivery

4. INTRODUCTION What is Drug Targetting? Targeted Drug Delivery systems (TDDS) are the delivery systems that release the drug at a preselected bio site in a controlled or Targeted manner. Targeted drug delivery systems (may also be referred to as smart drug delivery systems) is the currently used form of Drug delivery system where the pharmacologically active drug (or pro-drug in some cases) is targeted or is delivered specifically to the site of action.  

5. WHY TO TARGET A DRUG? To obtain desired therapeutic response. To avoid distribution of drug to other tissues which seems to be unnecessary, wasteful and a potential cause of toxicity. To prevent drug degradation and elimination that is done by the body defense systems such as opsonins in blood, liver and the kidney. To increase bioavailability and drug accumulation at the target. To prevent the drug from going into cells/tissues/organs where it is not needed.

6. HISTORY   In the year 1981, Gregoriadis described Drug Targeting using novel drug delivery system as ‘old drug in new clothes’ . The concept of designing targeted delivery system has been originated from the “ Paul Ehrlich ” a German Nobel laureate, proposed the idea of drug delivery in the form of ‘ magic bullet ’ in 1907. He described targeted drug delivery as an event where, “a drug –carrier complex/conjugate, delivers drug exclusively to the preselected target cells in a specified manner”.

7. PRINCIPLE & RATIONALE OF DRUG TARGETTING DRUG DRUG IN CARRIER Non Target site Target site Target site Non Target site Affinity-toxicity No affinity Low effect Targetted effect No affinity Low affect Inactivation/less therapeutic effect More therapeutic effect Bioenvironmental factors Bioenvironmental factors

8. Targeted drug delivery can be achieved by using carriers systems.Carriers are the drug vectors which transport and retain drug in route, which elute or deliver it within the target site. Carriers should have the following characteristics: They should cross anatomical barriers and in case of cancer chemotherapy, tumour vasculature. Recognized specifically and selectively by the target cells. The linkage of drug and ligand should be stable in the plasma, interstitial and other bio fluids. Non-toxic, Non immunogenic and biodegradable particulate and should release drug moiety inside the target organs, tissues or cells. CARRIERS

9. BASED ON THEIR ORIGIN CARRIERS CATEGORISED Endogenous High density lipoproteins Low density Lipoproteins Serum albumin Erythrocytes Exogenous Micro particulates Soluble polymeric biodegradable polymeric drug carriers

10. TYPES OF CARRIERS Colloidal Carriers 1.Vesicular System: Liposomes, Niosomes, Virosomes, Immunoliposomes 2. Microparticulate Systems: Microspheres, Nanoparticles Cellular Carriers Resealed Erythrocytes, Serum Albumin, Antibodies, Platelets, Leukocytes Supramolecular delivery Micelles, Reverse Micelle, Liquid Crystals, Lipoproteins (LDL,VLDL) Polymer based delivery Mucoadhesive, Biodegradable, Bio Erodible, Soluble Synthetic Carriers Macromolecular carriers 1.Proteins, Glycoproteins 2.Monoclonal Antibodies 3.Polysaccharides

11. Drug encapsulation in liposomes

12. LEVELS OF DRUG TARGETTING 1. Passive targetting 4. Inverse targetting 2. Active targetting 5 . Double targetting 3. Dual targetting 6. Combination targetting

13. PASSIVE TARGETTING Drug delivery systems which are targetted to systemic circulation are categorized as Passive delivery systems . In this technique, drug targeting occurs because of body’s natural response to the physicochemical characteristics of the drug or drug carrier systems. The ability of some colloid to be taken up by the Reticulo Endothelial Systems (RES) especially in liver and spleen made them ideal substrate for passive hepatic targeting of drugs.

14. ACTIVE TARGETTING In this approach carrier system bearing drug reaches to specific site on the basis of modification made on its surface rather than natural uptake by RES. Surface modification technique include coating of surface with either a bioadhesive , nonionic surfactant or specific cell or tissue antibodies ( i.e. monoclonal antibodies ) or by albumin protein .

15. The 3 levels of drug targeting First level to the organ , e.g. liver . Second level to the particular type of tissue within the organ , tumour . Third level selective uptake by the diseased cell , e.g. specific tumour cells. Also target invading organism/foreign body, e.g. HIV The higher the level the more efficacious, however more complicated to achieve . 1 st level - Liver 2 nd level- Tumour 3 rd level – uptake by the diseased cell

16. CONCLUSION

17. Active Targetting involves Ligand mediated targetting Physical targetting Ligand mediated targetting : A ligand is some molecule which we attach to the drug delivery system, which acts as a homing device and takes the delivery system to the target. All the carrier systems in general are colloidal in nature. Some examples of ligands used are antibodies, selectins , integrins , transferring, vitamins, hormones and low density lipoproteins. An example of this approach is “folate receptor targeting”. Advantages : 1. Site specificity. 2. Improved pharmaco -kinetics. 3. Avoidance of Multi- Drug Resistance. 4. Avoiding RES uptake.

18. LIGAND MEDIATED TARGETTING

19. B. Physical targetting : In this, some characteristics of environment (pH, temperature, ionic strength, ultrasound, light intensity, electric field, magnetic field…) are used to localize the drug carrier to the predetermined site. It is based on the fact that certain pathological areas differ from natural tissues in their pH and temperature. The First approach reported is the temperature sensitive liposomes in the vicinity of a tumour by Weinstein and coworkers . Yatwin and coworkers had reported on pH sensitive liposomes for selective release of contents at low pH. DUAL TARGETTING In this targeting approach carrier molecule itself have 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 thus synergistic effect of drug conjugate was observed.

20. INVERSE TARGETTING Passive uptake of colloid carrier by RES has been avoided hence the process is referred to as inverse targeting. To achieve inverse targeting RES normal function is suppressed by pre injecting large amount of blank colloidal carriers or macromolecules like dextran sulphate . This type of targeting is an effective approach to target drugs to non- RES organs . Lee and coworkers1995 , suggested inverse targeting of drugs to the sites other than RES rich organs by coating lipid micro emulsion with poloxamer 308 .

21. DOUBLE TARGETTING When temporal and spatial methodologies are combined to target a carrier system, then targeting may be called double targeting. Mew and coworkers studied on double targeting studies and reported haematoporphyrin (HP) – anti- M-1 antibody conjugates for the suppression of tumour following incandescent light exposure. Controlled release of drug -sustained release -stimuli responsive release -self regulating release Drug targeting -Active targeting -Passive targeting Double targeting

22. COMBINATION TARGETTING Petit and Gombtz have suggested the term combination targeting for the site specific delivery of proteins and peptides . These targeting systems are equipped with carriers, polymers and homing devices of molecular specificity that could provide direct approach to the target site . Approaches used in combination targeting are: Physical (permeation enhancing ) Chemical (prodrug approach) Carrier encapsulation

23. PROBLEMS ASSOCIATED WITH DRUG TARGETTING Rapid clearance of target systems especially antibody targeted carriers . Immune reactions against intravenous administered carrier systems. Problem of insufficient localization of targeted systems into tumour cells. Target tissue heterogenesity . Diffusion and redistribution of released drug leading to non-specific accumulation.

24. ADVANCED CARRIERS FOR TARGETTING DRUGS QUANTUM DOTS: Quantum dots are miniscule semiconductor particles that can serve as sign posts of certain types of cells or molecules in the body. These has potential of targetting cancerous drugs. MAGNETIC NANOPARTICLES:

25. Agnihotri J, ShubhiniS.Targeting : New Potential Carriers for Targeted Drug Delivery System. International J of Pharmaceutical Sciences Review and Research.2011; 8: 117-123 . Vyas.S.P,Khar R.K. Targeted & Controlled Drug Delivery, Novel Carrier Systems. First edition.CBS Publishers & Distributors. New Delhi; 2004: 487-511. Chien Y.W . Novel drug delivery systems, Drugs and the Pharmaceutical Sciences. New York; (2008 ). Muller R , Keck C. Challenges and solutions for the delivery of biotech drugs a review of drug nanocrystal technology and lipid nanoparticles. J of Biotechnology.2004;113:1-3. REFERENCES

26. Sarbjeet SG , Smriti K. International J of Advances in Pharmacy, Biology and chemistry. 2013 Mar; 2(1):130-136. Guptha M, Sharma V. Targeted drug delivery system: A Review . Research J of Chemical Sciences.2011 May;1(2):135-137. Karanth H, Murthi SR. Nanotechnology in Brain targeting.International J of Pharmaceutical sciences & nanotechnology.2008 june;1:9-24. Vladimir P. Drug Targeting. European J of Pharmaceutical sciences. 200 july ; 11: 81-91.

27. Querries

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