A PRESENTATION ON
DRUG TARGETING
Presenter
Fahad Hussain
M. Pharm in Clinical Pharmacy &
Pharmacology,
Department of Pharmacy
Noakhali Science and Technology
DRUG TARGETING
Background
Problems associated with Systemic Drug Administration
Even bio-distribution of pharmaceuticals throughout the
body
The lack of drug specific affinity toward a pathological
site
The necessity of a large total dose of a drug
Non-specific toxicity and other adverse side-effects.
isnt there any solution
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DRUG TARGETING
Targeted drug delivery 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.
Objective
Provide therapeutic concentration of drugs at the site of
action
Reduce systemic toxicity
Increase patient compliance
This improves efficacy of the drug while reducing side
effects.
ADVANTAGES OF DRUG TARGETING
Drug administration protocols may be simplified.
Drug quantity required to achieve a therapeutic effect
may be greatly reduced as well as the cost of therapy.
Drug concentration in the required sites can be
sharply increased without negative effects on nontarget compartments.
CLASSIFICATION OF DRUG TARGETING
Drug targeting has been classified into three types:
First Order
It refers to restricted distribution of the drug-carrier system to the
capillary bed of a predetermined target site, organ or tissue.
Compartmental targeting in lymphatics*, peritoneal cavity,
cerebral ventricles, lungs, joints, eyes, etc.
Second Order
The selective delivery of drugs to a specific cell type such as
tumor cells and not to the normal cells is referred as second
order drug targeting. The selective drug delivery to the Kupffer
cells in the liver** exemplifies this approach.
Third Order
The third order targeting is defined as drug delivery specifically to
the intracellular site of target cells. The receptor based ligandmediated entry of drug complex into a cell by endocytosis,
lysosomal degradation of carrier followed by release of drug
intra-cellularly or gene delivery to nucleolus is an example for
this approach.
* A network of vessels that conveys electrolytes, water, proteins, etc in the form of lymph from the tissue fluids to the
Drug Targeting
Passive Targeting
Leaky Vasculature
Tumor microenvironment
Direct local
application
Active targeting
Carbohydrate targeted
Receptor targeted
Antibody targeted6
DRUG TARGETING
Principal schemes of drug targeting currently investigated in
various experimental and clinical settings include:
Direct
application of the drug into the affected zone (organ,
tissue)
Passive
accumulation of the drug through leaky vasculature
(tumors, infarcts, inflammation)
physical
targeting based on abnormal pH and / or
temperature in the target zone, such as tumor or inflammation
(pH- and temperature-sensitive drug carriers)
Magnetic targeting of drugs attached to paramagnetic carriers
under the action of external magnetic field
Use
of vector molecules possessing high specific affinity
toward the affected zone
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DRUG TARGETING
The parameters determining the efficacy of drug
targeting:
Size of the target
Blood flow through the target
Number of binding sites for the
drug carrier within the target
Number and affinity of targeting moieties
targeted drug/
PASSIVE TARGETING APPROACHES
Take advantage of natural anatomical structures or physiological processes,
which direct carrier in vivo distribution
Pathophysiological factors Inflammation, Infection, EPR effect
Physicochemical factors
Size, Molecular weight
Anatomical opportunities
Catheterization, Direct injection
Chemical approaches
Prodrugs, Chemical delivery systems
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Fig: Spontaneous drug accumulation in `leaky' areas
ACTIVE TARGETING APPROACHES
Carrier specificity can be enhanced, through surface
functionalization with site-directed ligands which bind or
interact with specific tissues
Biochemical targets Organs, Cellular, Organelles,
Intracellular
Physical/External Stimuli
Ultrasound, Magnetic field
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MAIN APPROACHES TO TARGETING
Retrometabolic Systems:
Individual drug molecules chemically modified to
target particularly to the disease site.
Carrier Based Systems:
Drug is first packaged non-covalently into a
synthetic Carrier that is then targeted to the
disease site.
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DRUG TARGETING: PRODRUGS
Compounds that undergo biotransformation prior to
exhibiting pharmacological effect
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PRODRUG CONTINUING:
OVERCOMING BARRIERS
Chemically linking pro-moiety to form prodrug
Biotransformation
Release of parent drug
Barrier is circumvented
Examples:
6-Monoacetylmorphine (6-MAM) is a heroin metabolite which
converts into active morphine in vivo.
Prednisone, a synthetic cortico-steroid drug, is bioactivated by
the liver into the active drug prednisolone.
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DRUG TARGETING: MAGNETIC DRUG TARGETING
The Biophysical Targeting Technique
Using magnetic nanoparticles (ferrofluids)
Enhancing efficacy
Minimum side effects
Ferromagnetic element (e.g. an implant) is placed in a
magnetic field, it becomes magnetically energized
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MAGNETIC DRUG TARGETING CONTINUING:
GUIDED DRUG
DELIVERY
Solid tumor
Apply magnetic
field to
concentrate
particles
Modulate field to
release drug
from particles
Other options:
1 - Direct injection
into tumor site
2 - Coating NMP with
antibodies to target
Inject NMPs IV,
NMP will circulate
through the blood
stream
Ability to add
localized heating
combined with
drug delivery
MAGNETIC DRUG TARGETING CONTINUING:
ADVANTAGES
Magnetic drug targeting is used to treat malignant
tumors loco-regionally without systemic toxicity.
Magnetic particles used as carrier system for a variety
of anticancer agents, e.g. radionuclides, cancer
specific antibodies, and genes
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DRUG TARGETING: LIPOSOMES
These are vesicular concentric structures, range in size from a nanometer
to several micrometers, containing a phospholipids bilayer and are
biocompatible, biodegradable and non immunogenic.
Liposomes have generated a great interest because of their
versatility and have played a significant role in formulation of potent
drugs to improve therapeutics. Enhanced safety and efficacy have
been achieved for a wide range of drug classes, including antitumor
agents, antiviral, antimicrobials, vaccines, gene therapeutics etc.
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Bind
chromosomal
DNA in
target tumor
cell
Specifically
binding to
tumor cell
TWO-STEPS
TARGETING
DRUG TARGETING: TRANSDERMAL APPROACH
Transdermal
drug
delivery
system
is
topically
administered medicaments in the form of patches that
deliver drugs for systemic effects at a predetermined and
controlled rate.
A transdermal drug delivery device, which may be of an
active or a passive design, is a device which provides an
alternative route for administering medication. These
devices allow for pharmaceuticals to be delivered across
the skin barrier.
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TRANSDERMAL APPROACH CONTINUING:
In theory, transdermal patches work very simply. A drug is applied in
a relatively high dosage to the inside of a patch, which is worn on
the skin for an extended period of time. Through a diffusion
process, the drug enters the bloodstream directly through the skin.
Since there is high concentration on the patch and low concentration
in the blood, the drug will keep diffusing into the blood for a long
period of time, maintaining the constant concentration of drug in
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the blood flow.
DRUG TARGETING: BRAIN TARGETED DRUG DELIVERY SYSTEM
The brain is a delicate organ, and evolution built very efficient ways to protect
it. The delivery of drugs to central nervous system (CNS) is a challenge in
the treatment of neurological disorders.
Drugs may be administered directly into the CNS or administered
systematically (e.g., by intravenous injection) for targeted action in the
CNS. The major challenge to CNS drug delivery is the blood-brain barrier
(BBB), which limits the access of drugs to the brain substance.
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Fig: Central Nervous System-selective Estrogens: A Safe Estrogen Therapy
BRAIN TARGETED DRUG DELIVERY SYSTEM CONTINUING:
Advances in understanding of the cell biology of the BBB
have opened new avenues and possibilities for improved
drug delivery to the CNS.
Various strategies that have been used for manipulating
the blood-brain barrier for drug delivery to the brain
include osmotic and chemical opening of the blood-brain
barrier as well as the use of transport/carrier systems.
Other strategies for drug delivery to the brain involve
bypassing the BBB. Various pharmacological agents have
been used to open the BBB and direct invasive methods
can introduce therapeutic agents into the brain substance.
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CONCLUSION
Research related to the development of targeted drug delivery
system is now a day is highly preferred and facilitating field of
pharmaceutical world. It has crossed the infancy period and
now touching height of growths from the pharmacy point of
view.
Targeted delivery of drugs, as the name suggests, is to assist
the drug molecule to reach preferably to the desired site. The
inherent advantage of this technique has been the reduction
in dose & side effect of the drug.
Overall it may be concluded with the vast database of
different studies, the science of site specific or targeted
delivery of these drugs has become wiser. Manifestation of
these strategies in clinical now seems possible in near future.
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