TARGETED DRUG DELIVERY SYSTEMS 1.pptx123

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1. TARGETED DRUG DELIVERY SYSTEMS : CONCEPTS, EVENTS AND BIOLOGICAL PROCESS INVOLVED IN DRUG TARGETING PRESENTED BY, GADHE ROHIT M PHARM 1ST –YEAR DEPT OF PHARMACEUTICS

2. DEFINITION BASIC CONCEPTS OF DRUG TARGETING BIOLOGICAL PROCESSES AND EVENTS INVOLVED IN DRUG TARGETING REFERENCES CONTENTS

3. DEFINITION : Selective and effective localization of a pharmacologically active moiety at predefined targets in the therapeutic concentration, while restricting its access to non–targets is called drug targeting. It minimizes toxic effects and maximizes the therapeutic index. TDDS concentrates the medication in the tissue of interest or the targeted tissue and reduces the relative concentration of the medication in the remaining tissues. TARGETED DRUG DELIVERY SYSTEMS

4. BASIC CONCEPTS OF DRUG TARGETING Selective drug delivery improves the benefit/risk ratio associated with drugs. Ideally a drug should possess high therapeutic index, high efficacy and reduced toxicity. But many chemotherapeutic agents have narrow therapeutic index. This can be overcome by three approaches COMMON APPROACHES TO TDDS : To control the distribution of the drug by incorporating into a carrier. Altering the structure of drug at molecular level. Controlling the input of drug into bio environment to ensure programmed bio distribution.

5. Ideal features of a carrier : Able to cross the anatomical barriers and tumour vasculature in case of tumour therapy. Should be recognized specifically and selectively by the target cells. Should be non-toxic, non-immunogenic and biodegradable. After recognition and internalization, the carrier should release the drug moiety inside the target organs. Carriers : Carriers play an immense role in drug targeting. They act as the drug vectors which transport, retain, interact and deliver the drugs to the target.

6. Types of carriers used in TDDS Colloidal carriers Vesicular systems E.g. liposomes, biosomes, pharmacosomes etc. Microparticulate systems E.g. Nanoparticles, magnetic microspheres, albumin microspheres etc. 2. Cellular carriers E.g. Resealed erythrocytes, serum albumin, antibodies etc. 3. Macromolecular carriers E.g. Proteins, glycoproteins, toxins, immunotoxins etc. 4. Polymer based systems E.g. Polyacrylates, Polyglycolic acid, Polyvinylpyrrolidone etc.

7. Drug release does not effect the drug 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 and no carrier induced modulation of diseased state. • The preparation of the delivery system should be easy or reasonably simple, reproductive and cost effective. IDEAL CHARACTERISTICS:-

8. 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. ADVANTAGES

9. DISADVANTAGES 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. • Requires highly sophisticated technology for the formulation. • Requires skill for manufacturing storage, administration. • Drug deposition at the target site may produce toxicity symptoms. •Difficult to maintain stability of dosage form. E.g.: Resealed erythrocytes have to be stored at 40 C. • Drug loading is usually law. E.g. As in micelles. Therefore it is difficult to predict /fix the dosage regimen.

10. Cellular Uptake and Processing Transport across the epithelial Barrier Extravasation Lymphatic Uptake BIOLOGICAL PROCESS AND EVENTS IN DRUG TARGETING :-

11. 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

12. Phagocytes^^^^ rest of the cells • opsosins immunoglobulin G complement C3b fibronectin • dysopsonins IgA & sIgA impart degree of hydrophilicity>>>decrease the uptake.

13. 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.

14. TRANSPORT ACROSS 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 in varied forms. Three layer physiology:- Epithelial Lamia propria Basal lamina • Low molar mass drugs cross the above by passive diffussion carrier mediated systems and by selective and non-selective endocytosis.

15. The polar materials diffuse through tight junctions of epithelial cells. • Passive transport is usually higher in damaged mucosa where as active transport depends on structural integrity of epithelial cells. • Positively charged particles showed increased uptake than negatively charged counterparts. • Absoption of drugs from buccal is via transcellular and paracellular the later being dominant. Some examples are:- • for example:-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 it first undergo uterine pass effect suggesting that the vaginal route can be used to target the uterus .

16. EXTRAVASTATION :- 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

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

18. 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.

19. Factors know to influence the clearance of drugs from interstitial sites are:- 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.

20. REFERENCES:- 1. Muller, R; Keck, C (2004). "Challenges and solutions for the delivery of biotech drugs – a review of drugnanocrystal technology and lipid nanoparticles". Journal of Biotechnology 113 (1–3): 151–170. doi:10.1016/j.jbiotec.2004.06.007 2. Target-Oriented Drug Delivery Systems(9) by Vijay kumar Modern Pharmaceutics Volume 2 Applications and Advances; Fifth edition edited by Alexander T. Florence Pg.no 329-342. 3. Encyclopaedia of controlled delivery by Edith Mathiowitz 4. S.P Yyas and R.K Khar Controlled drug Delivery concepts and advances Vallabh prakashan first edition

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