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PREPARED BY :
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.
• Provide therapeutic
concentration of drugs at the
site of action
• Reduce systemic toxicity
• Increase patient compliance
Classification of Drug
TargetingDrug targeting has been classified into three
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,
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
The third order targeting is defined as drug delivery
Passive Targeting Active targeting
Direct local application
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
The parameters determining the
efficacy of drug targeting:
• Size of the target
• Blood flow through the target
• Number of binding sites for the
targeted drug/ drug carrier within the
• Number and affinity of targeting
approachesPathophysiological factors – Inflammation, Infection, EPR effect
Physicochemical factors – Size, Molecular weight
Anatomical opportunities – Catheterization, Direct injection
Chemical approaches – Prodrugs, Chemical delivery
approachesCarrier specificity can be enhanced, through surface
functionalization with site-directed ligands which bind or
interact with specific tissues
Biochemical targets – Organs, Cellular, Organelles,
Physical/External Stimuli – Ultrasound, Magnetic
Main Approaches to Targeting
Individual drug molecules chemically
modified to target particularly to the
Carrier – Based Systems:
Drug is first packaged non-covalently into
a synthetic Carrier that is then targeted
to the disease site.
ProdrugsCompounds that undergo biotransformation
prior to exhibiting pharmacological effect
Chemically linking pro-moiety to form prodrug
Release of parent drug
Barrier is circumvented
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 Targeting: Magnetic
•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
The Biophysical Targeting
field to concentrate
Modulate field to
release drug from
Inject NMPs IV,
NMP will circulate
through the blood stream
1 - Direct injection into
2 - Coating NMP with
antibodies to target
Magnetic Drug Targeting Continuing: Guided Drug Delivery
Ability to add
combined with drug
Magnetic Drug Targeting Continuing:
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,
These are vesicular concentric structures, range in size from a nanometer to several
micrometers, containing a phospholipids bilayer and are biocompatible, biodegradable and
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.
DNA in target
ApproachTransdermal 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.
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 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.
Fig: Central Nervous System-selective Estrogens: A Safe Estrogen Therapy
Brain targeted drug delivery system
Advances in understanding of the cell biology of the BBB have
opened new avenues and possibilities for improved drug delivery to
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
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.
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
Transporters are those proteins that carry either
endogenous compounds or xenobiotics across biological
They can be classified into either efflux or uptake
proteins, depending on the direction of transport.
The extent of expression of genes coding for transport
proteins can have a profound effect on the bioavailability
and pharmacokinetics of various drugs.
Additionally, genetic variation such as single-nucleotide
polymorphisms (SNPs) of the transport proteins can
cause differences in the uptake or efflux of drugs.
In terms of cancer chemotherapy, tumor cells
expressing these proteins can have either enhanced
sensitivity or resistance to various anticancer drugs.
Transporters that serve as efflux pumps on a cell
membrane can remove drugs from the cell before
they can act.
Transport proteins that are responsible for the vital
influx of ions and nutrients such as glucose can
promote growth of tumor cells if overexpressed, or
lead to increased susceptibility for a drug if the
transporter carries that drug into the cell.
Importance of Drug
Role in overall disposition of drugs to the
Significant determinant of drug-drug
Variability in drug response
Types of drug
Two types of transporter :
ATP binding Cassette (ABC) – Found in ABCB,
ABCD and ABCG family. Associated with
multidrug resistance (MDR) of tumor cells
causing treatment failure in cancer.
Solute Carrier (SLC) – Transport varieties of
solute include both charged or uncharged
ATP Binding Cassette Solute Carrier
Efflux transporter Influx / bidirectional
Utilize energy from ATP Electrochemical
gradient / facilitated
Primary active Secondary active
Subfamilies : ABCA,
ABCB, ABCD, ABCE,
Subfamilies ; SLC15,
• ATP binding cassette sub family B member-
1 (ABCB 1)
• Multidrug resistance protein 1 (MDR1)
• Transport various molecules, including
xenobiotic, across cell membrane
• Extensively distributed and expressed
throughout the body
Function of P-glycoprotein
Site of transportation Function
Liver – Bile Elimination
Kidney - Urine Excretion
Placenta – Maternal blood Protect fetal from drug
Intestine – Intestinal lumen Reduce drug absorption into
Brain – Blood Monitor drug access to the
Mechanism of P-
① Substrate bind to P-gp form the inner
leaflet of the membrane
② ATP binds at the inner side of the
③ ATP is hydrolyzed to produce ADP and
④ Substrate is excreted outside the cell
P-gp is a multidrug resistant protein (MDR)
Role of P-gp is significant in tumor cells.
Expression of P-gp in tumor cells reduces the
accessibility of cytotoxic drugs by eliminating them
in various pathways. Hence, P-gp may act as a
major barrier to effective drug treatments.
Over expression of P-gp in limit the treatment for
cancer, AIDS, Alzheimer’s and epilepsy.
Dean M, Hamon Y, Chimini G (July 2001). "The human ATP-binding cassette
(ABC) transporter superfamily”
Hediger MA, Romero MF, Peng JB, Rolfs A, Takanaga H, Bruford EA (2004).
"The ABCs of solute carriers: physiological, pathological and therapeutic
implications of human membrane transport proteins: Introduction”
Dean, Michael (2002-11-01). "The Human ATP-Binding Cassette (ABC)
Peter N Bennett, Morris J Brown, Pankaj Sharma, 11th Edition (2012).
Department of Drug Metabolism, Merck Research Laboratories (Nov 2003).
“Clinical relevance of P-glycoprotein in drug therapy”