Targeted drug delivery system

Here explained about Targeted Drug Delivery System

1. Targeted Drug Delivery System FACILITATED TO: Dr. Anita Desai HOD Dept.of Pharmaceutics H.S.K.College of Pharmacy Bagalkot PRESENTED BY: Ismail Makanadar MPhram 2 nd Sem Dept.of Pharmaceutics H.S.K.College of Pharmacy Bagalkot 1

2. Contents Introduction Concept Ideal Characters Advantages Carrier or markers Events and Biological Processes 2

3. INTRODUCTION : ‘Targeted drug delivery system is a special form of drug delivery system where the 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.’ 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. This improves efficacy and reduce side effects. 3

4. OBJECTIVE : To achieve a desired pharmacological response at a selected sites without undesirable interaction at other sites, there by the drug have a specific action with minimum side effects & better therapeutic index. Ex- In cancer chemotherapy and enzyme replacement therapy. 4

5. REASON FOR DRUG TARGETING : 5

6. IDEAL CHARACTERISTICS : It should be nontoxic, biocompatible, biodegradable, and physicochemical stable invivo and invitro . Restrict drug distribution to target cells or tissues or organs and should have uniform capillary distribution. Controllable and predicate rate of drug release. Drug release does not effect the drug action. Therapeutic amount of drug release. Carriers used must be bio-degradable or readily eliminated from the body without any problem and no carrier induced modulation of diseased state. The preparation of the delivery system should be easy or reasonably simple, reproductive and cost effective. 6

7. ADVANTAGES : Drug administration protocols may be simplified. Toxicity is reduced by delivering a drug to its target site, there by reducing harmful systemic effects. Drug can be administered in a smaller dose to produce the desire effect. Avoidance of hepatic first pass metabolism. Enhancement of the absorption of target molecules such as peptides and particulates. Dose is less compared to conventional drug delivery system. No peak and valley plasma concentration. Selective targeting to infections cells that compare to normal cells. 7

8. CARRIER OR MARKERS : T a r get e d drug del i very can be ach i eved by usi ng carrier system . Carrier is one of the special molecule or system essentially required for effective transportation of loaded drug up to the pre selected sites . 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. Pharmaceutical carriers : Polymers Microcapsules Microparticles Lipoproteins Liposomes Micelles 8

9. Events and biological process involved in drug targeting. 9

10. Cellular Uptake and Processing Following administration low molar mass drugs can enter into or pass through various cells by simple diffusion process. Targeted drug delivery usually have macro molecular assemblies hence cannot enter by such simple process. Hence take up by a process called ENDOCYTOSIS Steps involved : Internalization of the plasma membrane Concomitant with engulfment of extracellular material 10

11. 11

12. Compared with phagocytosis pinocytosis is a universal phenomenon in all the cells pinocytosis does not require any external stimulus Pinocytosis is divided into two types: Fluid phases pinocytosis Adsorptive pinocytosis Compared with phagocytosis fluid phase pinocytic capture of molecules is relatively slower being directly proportional to the concentration and size dependant 12

13. Transport across the epithelial barrier The oral, buccal , nasal, vaginal, and rectal cavities are internally lined with one or more layers of epithelial cells Depending on the position and function in the body epithelial cells can be varied forms Three layer physiology: Epithelial Lamia propria Basal lamina Low molar mass drugs cross the above by passive difussion carrier mediated systems selective and non-selective endocytosis 13

14. The polar materials diffuse through tight junctions of epithelial cells Passive transport is usually higher in damaged mucosa whereas active transport depends on structural integrity of epithelial cells Positively charged particles showed increased uptake than negatively charged counterparts. Absoption of drugs from buccal via transcellular and paracellular later being dominant • Ex-vaginal cavity could be an effective delivery site for certain pharmaceuticals Such as calcitonin for the treatment of postmenopausal osteoporosis • It was demonstrated that when delivered vaginally first undergo uterine pass effect suggesting that the vaginal route can be useed to target to the uterus 14

15. Extravasation Many diseases result from the dysfunction of cells located outside the cardiovascular system thus for a drug to exert its therapeutic effects it must exit from the central circulation this process of trans vascular exchange is called Extravasation which is governed by blood capillary walls Factors that control permeability of capillaries Structure of the capillary wall Pathological condition Rate of blood and lymph supply Physicochemical factors of drug 15

16. • The structure of the blood capillary varies in different organs tissues. • It consists of a single layer of endothelial cells joined together by intercellular juctions • Depending on the morphology and continuity of the endothelial layer and the basement membrane blood capillaries are divided into • Continuous • Fenestraded • Sinusoidal 16

17. 17

18. Continuous capillaries are common and widely distributed in the body exhibit tight inter endothelial junctions and an uninterrupted basement membrane Fenestrated capillaries shows interendothelial gaps of 20-80nm Sinusoidal capillaries show inter endothelial gaps of 150nm Depending on the tissue or organ the basal membrane is either absent ex-liver or present in discontinuous ex-spleen and bone marrow Macromolecules can transverse the normal endothelium by passive process such as nonspecific fluid phase trans capillary Pinocytosis and passage through inter endothelial junctions gaps or fenestrate or by receptor-mediated transport systems 18

19. • Organs such as the lung with very large surface areas have a proportionately large total permeability and consequently a high extravasation • Depends on charge shape, size, HLB, characteristics of macromolecules • The endothelium of brain is the strongest of all endothelia formed by continous nonfenestrated endothelial cells which show no pinocytic activity • Soluble macromolecules permeate the endothelial barrier more readily than particulate macromolecules the rate of movement of fluid across the endothelium appears to be directly related to the diff between the hydrostatic and osmotic forces 19

20. Lymphatic Uptake Following extravasation drug molecules can either reabsorb into the blood stream directly or enter into the lymphatic system and return with the lymph to the blood circulation Also drugs administered by subcutaneous intracellular transdermal peritoneal routes can reach the systemic circulation by lymphatic system 20

21. 21

22. • Factors know to influence the clearance of drugs from interstitial sites Route of administration Size and surface characteristics of particles Formulation medium The composition and pH of the interstitial fluid and Disease within the interstitium • The direct delivery of drugs into lymphatics has been proposed as a potential approach to kill malignant lymphoid cells located in lymph nodes 22

23. STRATEGIES OF DRUG TARGETING 1) 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. 23

24. 24 2) 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 defence mechanism. This type of targeting is a effective approach to target drug to non-RES organs.

25. 25 3) 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. 3 Types First order targeting (organ compartmentalization). Second order targeting (cellular targeting). Third order targeting (intracellular targeting).

26. 26 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.

27. 27 6) 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. 7) 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. w her eas te m poral del i very re fers to controlling the rat e o f drug delivery to target site.

28. References: S.P Yyas and R.K Khar Controlled drug Delivery concepts and advances Vallabh prakashan first edition www.wikipedia.com 28

29. Thank You 29