‘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.’
3. ON
• 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 and not to the non-target organs or tissues
or cells.
• The drug may be delivered:
To the capillary bed of the active sites,
To the specific type of cell (or) even an intracellular
region. Ex- tumour cells but not to normal cells,
To a specific organ (or) tissues by complexing with the
carrier that recognizes the target
Introduction
4. • It is a method of delivering medication to a patient in a
manner that increases the concentration of the medication
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.
‘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.’
6. ON
Reasons for Site specific delivery of drugs
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. ON
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 in enzyme
replacement therapy.
OBJECTIVES
8. ON
Targeted drug delivery system should be-
HOW??
• Biochemically inert (non-toxic)
• Non-immunogenic.
• Both physically and chemically stable in vivo and in
vitro.
• Restrict drug distribution to target cells or tissues or
organs
• Should have uniform capillary distribution.
• Controllable and predicate rate of drug release.
IDEAL CHARACTERISTICS
9. ON
• 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
10. ON
ADVANTAGES
•Control of drug delivery on to a particular site or
vicinity with predetermined or expected release
kinetics.
• 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 toinfections cells that compare
to normal cells.
DISADVANTAGES
• Expensive
• Technical skill required
• Stability issues both
Chemical and physical
biological as well
• Yield comparatively very less
Advantages and Disadvantages
Targeted drug delivery systems
11. Biological processes and events involved in drug
targeting
• Cellular Uptake and Processing
• Transport across the epithelial barrier
• Extravasation
• Lymphatic Uptake
12.
13. ON
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
14. ON
Cellular Uptake and Processing
• Phagocytes^^^^ rest of the cells opsosins immunoglobulin G complement C3b
fibronectin.
• dysopsonins IgA & sIgA impart degree of hydrophilicity>>>decrease the uptake
15. ON
Cellular Uptake and Processing
• 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:
1. Fluid phases pinocytosis
2. Adsorptive pinocytosis
• Compared with phagocytosis fluid phase pinocytic
capture of molecules is relatively slower being directly
proportional to the concentration and size dependant
16. ON
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 ans selective and
non-selective endocytosis
17. ON
Transport across the epithelial barrier
• 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 via transcellular and
paracellular later being dominant.
18. ON
Transport across the epithelial barrier
• Some proposals
• 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
19. ON
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
20. ON
Extravasation
• 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
22. ON
Extravasation
• Continuous capillaries are common and widely
distributed in the body exhibit tight inter endothelial
junctions and an uninterrupted basement membrane
• Fenestrated capillaries shows inter-
endothelial 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.
23. ON
Extravasation
• 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
• 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.
24. ON
Extravasation
• 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.
25. ON
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.
27. ON
Lymphatic Uptake
• 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.
28. ON
References:
1. Muller, R; Keck, C (2004). "Challenges and solutions for the
delivery of biotech drugs – a review of drug nanocrystal
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.
