A brief introduction of targeted drug delivery system and bological processes involved in targeted drug delivey system.

1. TARGETED DRUG
DELIVERY SYSTEM
Prepared by: Pragya Sharma
M. Pharma 2nd Sem. (Pharmaceutics)
B.N. College of Pharmacy, Udaipur
Guided by : Dr.Kamal S Rathore

2. CONTENTS:
• Introduction
• Objective
• Ideal characteristics
• Concept of drug targeting
• Carriers and markers
• Events and biological process involved in drug targeting
• Advantage and disadvantage

3. Introduction:
• It is a special form of drug delivery system where the pharmacologically active agent or medicament is selectively
targeted or delivered only to its site of action or absorption not to the non- target organ or tissues or cells.
• It is a method of delivering medication to a patient in a manner that increases the concentration of medication in
some part of the body relative to others.
• Targeted drug delivery seeks to concentrate the medication in the tissue of interest while reducing the relative
concentration of medication in the remaining tissues.
• This improves the efficiency and reduce side effects .

4. The drug may be delivered :
• To the capillary bed of the active site.
• To the specific type of cell (or) even an intracellular region ex; tumour cell but not to normal cells.
• To a specific organ (or) tissue by complexion with the carrier that recognizes the target.
OBJECTIVE :
• To achieve a desired pharmacological at a selected site without undesirable interaction at other sites, thereby the drug
have a specific action with minimum side effects and better therapeutic index.
• Example: In cancer chemotherapy and enzyme replacement therapy.

5. Ideal characteristics :
• It should be nontoxic ,biocompatible, biodegradable, and physiochemical stable in vivo and in vitro
• Restrict drug distribution to target cells or tissues or organs and should have uniform capillary distribution.
• Controllable and predicate rate of dug release
• Drug release o not effect the drug action
• Therapeutic mount of drug release.
• Minimal drug leakage during transit
• Carriers must be bio- degradable or readily elimination 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. Reason for drug targeting :
• In the treatment or prevention of diseases.
• Pharmaceutical drug instability in conventional dosage form solubility, biopharmaceutical low absorption, high
membrane bounding, biological instability, pharmacokinetic/pharmacodynamic short half life, large volume of
distribution, low specificity, clinical low therapeutic index.

7. Carriers and markers:
• Targeted drug delivery can be achieved by using 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 vi spacer moiety and
transport or deliver it into vicinity of target cell.
Pharmaceutical carriers:
Polymers
Microcapsules
Micro particles
Lipoproteins
Liposomes
micelles

8. Events and Biological Process Involved in Targeted drug delivery system :
1. Cellular uptake and processing
2. Transport across the epithelial barrier
3. Extravasation
4. Lymphatic uptake
1. 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 and EXOCYTOSIS
• Both requires energy.
• Large particles are transported across the membrane in membrane bound vesicles.

9. ENDOCYTOSIS:
• The process where a cell absorb extra cellular material by engulfing it with their cell membrane to form a vesicle which
is then pinched off intracellularly.
• This particles does not pass through the membrane it is simply engulfed and enclosed .

10. EXOCYTOSIS
• The reverse process where materials are expelled or secreted from a cell.
• This is used to read wastes and secreted substances(hormones) produced by the cell.
• It may be excretion or secretion.

11. PHAGOCYTOSIS
PHAGOCYTOSIS(solid particles-cell eating)
• This is carried out by special cell of mono nuclear phagocyte system called phagocytes by absorption of specific blood
component called “opsonins”.
• Phagocytic vacuole fuses with one or more lysosomes to form phagolysosomes.
• Digestion of particles occur by lysosomal acid hydrolysis, making drug available to exert its effect.

12. PINOCYTOSIS
PINOCYTOSIS (liquid- cell drinking)
• Pinocytosis (a form of endocytosis ) allows a cell to engulf large molecules and fluid that may be present in the
extracellular region.
• The cell membrane folds inward's, encloses the fluid o particle to be transported and then fuses to form a vesicle.
• The vesicle detaches from the membrane and moves to the interior of the cell.
• It is of two types:
Fluid phase pinocytosis
Receptor mediated pinocytosis

13. 2. Transport across epithelial barrier:
• Oral buccal, nasal, vaginal and rectal cavities are internally lined with one or ore layers of epithelial cells.
• Depending on position and function in body, these cells vary . These cells are extremely cohesive
• Absorption of low molecular weight dugs from oral route is well established.
• Various transport processed frequently dugs across epithelial barrier lining are,
• Passive diffusion
• Carrier mediated
• Endocytosis
• Additionally polar molecule can diffuse through tight junction of epithelial cells i.e paracellular route.
• Molecules less than 10 K.da are absorbed from nasal epithelium into systemic circulation in sufficient amount without
need of added materials.
• Large molecule proteins (e.g. human growth hormone) requires both penetration enhancer and isoadhesives.
• This flux enhancers deleterious effect
nasal mucosa and mucocilliary clearance

14. Overcome by
• Phospholipid,
Significant increase in absorption of macromolecules.
Biocompatible
Bioresorbable
No or less threat of toxicity
• Penetration enhancers
Improves intestinal absorption of peptides and other macromolecular drugs
These include
a) Chelators ; EDTA, citric acid salicylates etc.
b) surfactants; natural, semisynthetic and synthetic
c) Fatty acid and derivatives: e.g. oleic acid, sodium laurate, sodium caprate etc.
cyclodextrins
phospholipids

15. Factors influencing the absorption of drugs from gastrointestinal tract:
• pH
• Enzymes
• Surface area
• Microflora
• Transit time.

16. 3. Extravasation:
• For the drug to exert its therapeutic effects, it must move from the central circulation and interact with its extra vascular
or extravascular o extra vascular intracellular target. This process of transvascular exchange is called extravasation.
Extravasation is governed by:
Permeability through blood capillary
Rate of blood and lymph
Physiochemical factors like :
a) molecular shape, size and charge of drug
b) And its Hlb characteristics
Depending on the morphology and continuity of endothelial layer and basement membrane , blood
capillaries are of three types :
• Continuous
• Fenestrated
• sinusoidal

17. 1. Continuous capillaries :
• These are common and widely distributed in the body
• They exhibit tight interendothelial junctions and an uninterrupted basement membrane.
2. Fenestrated capillaries :-
• These show interendothelial gaps of 8-20 nm at regular intervals.
3. Sinusoidal capillaries:
• Show 150 nm of interendothelial gaps.
• Basal membrane is absent in sinusoidal capillaries of live and is discontinuous in spleen and bone marrow.

18. 4.Lymphatic uptake:
• Following extravasation, the drug molecules can either reabsorb into the blood stream directly by the enlarged post
capillary interendothelial cell pores found in most tissues or enter into the lymphatic system and then return with the
lymph to the blood circulation.
• Drugs administered through subcutaneous, intramuscular, transdermal and peritoneal routs reach the systemic
circulation by lymphatic system.

19. Lymphatic circulation:
• Lymphatic circulation is a path of minor importance in drug absorption into systemic circulation for the reasons:
1) The lymph vessel are less accessible than the capillaries.
2) The lymph flow is exceptionally slow.
• However fats, fat soluble vitamins and highly lipophilic drugs are absorbed through.
• Advantage of lymphatic absorption of drugs:
Avoidance of first pass metabolism
Compounds of high molecular weight (above 16,000) can be absorbed by lymphatic transport.
Targeted delivery of drugs to lymphatic system as in certain case of cancer is possible.

20. Advantages:
• Drug administration protocol may be simplified.
• Toxicity is educed by delivering a drug to its target site, there by reducing armful 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.

21. 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 drug.
• Requires highly sophisticated technology for the formulation.
• Requires skills 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 4 degree Celsius.

22. References :
• Researchgate.com targeted drug delivery systems.
• Targeted and controlled drug delivery (novel carrier systems), SP Vyas and R K Khar, CBS Publishers,2002.
• Progress in controlled and novel drug delivery systems by N K Jain, CBS publishers, 2008.