A presentation on drug targeting by Fahad Hussain, Editor of Pharma Mirror Magazine

1. A PRESENTATION ON
DRUG TARGETING
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Presenter
Fahad Hussain
M. Pharm in Clinical Pharmacy & Pharmacology,
Department of Pharmacy
Noakhali Science and Technology University.
www.PharmaMirror.com

2. 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.
isn’t there any solution
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3. 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.
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4. 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
non-target
compartments.
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5. 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 ligand-mediated
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 bloodstream.
** Phagocytic cells that line the sinusoids of the liver
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6. Drug Targeting
Passive Targeting
Leaky Vasculature
Tumor microenvironment
Direct local application
Active targeting
Carbohydrate targeted
Receptor targeted
Antibody targeted
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7. 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 temperaturesensitive 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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8. 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
carrier within the target
•
Number and affinity of targeting moieties
targeted drug/ drug
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9. 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

10. 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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11. 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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12. DRUG TARGETING: PRODRUGS
Compounds that undergo biotransformation prior to
exhibiting pharmacological effect
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13. 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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14. 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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16. MAGNETIC DRUG TARGETING CONTINUING: GUIDED
Solid tumor
Apply magnetic
field to concentrate
particles
Modulate field to
release drug from
particles
DRUG DELIVERY
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

17. MAGNETIC DRUG TARGETING CONTINUING:
ADVANTAGES

Magnetic drug targeting is used to treat malignant tumors locoregionally 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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18. 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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19. Bind
chromosomal
DNA in target
tumor cell
Specifically
binding to
tumor cell
TWOSTEPS
TARGETING

20. 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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21. 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 low21
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 the blood flow.

22. 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

23. 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 bloodbrain 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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24. 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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