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RENU RAWAT
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CONTENT
1. Introduction
2. Ideal characteristics
3. Carrier or markers
4. Strategies of drug targeting
5. Types of targeted drug delivery system
6. Advantages
7. Disadvantages
8. Targeted therapies that have been approved
9. Conclusion
10. References
INTRODUCTION
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.
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.
The drug may be delivered to:
1. The capillary bed of the active sites,
2. To the specific type of cell (or) even an intracellular region; Ex: Tumors cells but not to
normal cells,
3. To a specific organ (or) tissues by complexion with the carrier that recognizes the target.
OBJECTIVE:
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.
REASON FOR DRUG TARGETING:
1. Drug may arrive at a non-target organ.
2. Drug concentrations could be diluted to the point where it has no effect
3. Pharmaceutical drug instability in conventional dosage form
solubility,
biopharmaceutical low absorption,
high-membrane bounding,
biological instability,
pharmacokinetic / pharmacodynamics short half-life,
large volume of distribution,
low specificity,
Low therapeutic index.
IDEAL CHARACTERISTICS:
1. It should be nontoxic, biocompatible, biodegradable, and physicochemical stable in vivo
and in vitro.
2. It should restrict drug distribution to target cells or tissues or organs and should have
3.
4.
5.
6.
7.
CARRIER OR MARKERS:
Targeted drug delivery can be achieved by using carrier system. Carrier is one of the special
molecules or system essentially required for effective transportation of loaded drug up to the preselected sites. They are engineered vectors, which retain drug inside or onto them either via
encapsulation and/ or via spacer moiety and transport or deliver it into vicinity of target cell.
Pharmaceutical carriers:
1.
Polymers
2.
Microcapsules
3.
Microparticles
4.
Lipoproteins
5.
Liposomes
6.
Micelles
7.
Dendrimers
8.
Virosome
9.
Nanoparticle
found exceptional for tumor targeting as well as cytosolic delivery of entrapped drug or
genetic material.
6. Dual Targeting:
In this targeting approach carrier molecule itself have its own therapeutic activity and thus
increase the therapeutic effect of drug. For example, a carrier molecule having its own
antiviral activity can be loaded with antiviral drug and the net synergistic effect of drug
conjugate was observed.
7. Double Targeting:
Temporal and spatial methodologies are combined to target a carrier system, and then
targeting may be called double targeting. Spatial placement relates to targeting drugs to
specific organs, tissues, cells or even subcellular compartment whereas temporal delivery
refers to controlling the rate of drug delivery to target site.
Nanoparticle:
a. Nano Tubes: They are hollow cylinder made of carbon, atoms which can be filled and
sealed for potential drug delivery.
Application: Cellular scale needle for attaching drug molecule to cancer cells as an
electrode in thermo cells.
b. Nano wires: The nanowire pinpoint damage from injury and stroke, localize the cause of
seizures, and detect the presence of tumors and other brain abnormalities.
Application: Technique has potential as a treatment for Parkinson's and similar diseases.
c. Nanoshells: Nanoshells are hollow silica spheres covered with gold. Scientists can attach
antibodies to their surfaces, enabling the shells to target certain shells such as cancer
cells.
Application: Technique has potential for targeting cancerous drug.
d. Quantum dots: A quantum dot is a semiconductor nanostructure that confines the
motion of conduction band electrons, valence band holes or bound pairs of
conduction band electrons and valence band holes in all three spatial directions. The
ability to tune the size of quantum dots is advantageous for many applications and
it is one of the most promising candidates as vehicle for drug transportation with
its
in
f. Gold Nano: Particle Scientist uses gold nanoparticle to develop ultrasensitive detection
system for DNA and protein markers associated with many forms of cancer, including
breast prostate cancer.
Application: In cancer Treatment and Genetic engineering.
g. Nanocrystals: Nanocrystal is any Nano material with at least one dimension 100nm and
that is single crystalline. More properly, any material with a dimension of less than 1
micrometer, i.e., 1000 nanometers, should be referred to as a nanoparticle, not a
Nanocrystal. For example, any particle which exhibits regions of crystallinity should be
termed nanoparticle or nanocluster based on dimensions.
h. Nanobots: Nanorobotics is the technology of creating machines or robots at or close to
the microscopic scale of a nanometer (109meters). More specifically, Nanorobotics
refers to the still largely hypothetical nanotechnology engineering discipline of designing
and building nanorobots, devices ranging in size from 0.1-10 micrometers and
constructed of nano scale or molecular components.
Fig: Release of drug from amino dendrimers (PAMAM and PPI) depends on pH condition.
3) Liposomes: Liposomes are small artificially designed vesicles composed of phospholipid
bilayers surrounding with the size ranging from 20 to 10 000 nm. Many liposome
formulations are rapidly taken up by macrophages and this can be exploited either for
macrophage-specific delivery of drugs or for passive drug targeting which allow slow
release of the drug over time from these cells into the general circulation. The drug
molecules can either be encapsulated in aqueous space or intercalated into the lipid bilayers.
The extent of location of drug will depend upon its physico-chemical characteristics and
composition of lipids. Cationic liposomes and lipoplexes have been extensively researched
for their application in non -viral vector mediated gene therapy.
in genome grafting and cellular micro injection. A. Interaction of the virosomes with cell
surface receptors. B. Release of the encapsulated drug molecules in the target cell.
7) Transferosomes: A transferosomes, in functional terms, may be described as lipid droplets
of such deformability that permits its easy penetration through the pores much smaller than
the droplets size. Transferosomes is a supramolecular entity that can pass through a
permeability barrier and there by transport material from the other site. These are more
elastic than standard liposomes.
8) Lipoproteins: Lipid particles such as LDL and HDL containing a lipid and an apoprotein
moiety is termed as natural targeted liposomes and its core can be used to incorporate
lipophilic drugs or lipophilic pro-drugs and it does not require covalent bonding with the
drug. Modifications at the level of glycolipid incorporation can be used to introduce
new targeting moieties. The majority of the research on the use of LDL and HDL
particles has been done and improved at the level of targeting the drugs to the liver.
ADVANTAGES:
1. Drug administration protocols may be simplified.
2. Toxicity is reduced by delivering a drug to its target site, thereby reducing harmful
3.
4.
5.
6.
7.
8.
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.
DISADVANTAGES:
1.
2.
3.
4.
5.
6.
7.
8.
stored at 40 C.
9. Drug loading is usually law. E.g. As in micelles. Therefore it is difficult to predict /fix the
dosage regimen.
The FDA has approved targeted therapies for the treatment of some patients with the following
types of cancer:
Adenocarcinoma of the stomach or gastroesophageal junction: Trastuzumab Herceptin),
ramucirumab (Cyramza)
Basal cell carcinoma: Vismodegib (Erivedge)
Brain cancer: Bevacizumab (Avastin), everolimus (Afinitor)
Breast cancer: Everolimus (Afinitor), tamoxifen, toremifene (Fareston), Trastuzumab
(Herceptin),
fulvestrant
(Faslodex),
anastrozole
(Arimidex),
exemestane
(Aromasin),lapatinib (Tykerb), letrozole (Femara), pertuzumab (Perjeta), adotrastuzumab emtansine (Kadcyla), palbociclib (Ibrance)
Cervical cancer: Bevacizumab (Avastin)
Colorectal cancer: Cetuximab (Erbitux), panitumumab
(Avastin),ziv-aflibercept (Zaltrap), regorafenib (Stivarga)
(Vectibix),
bevacizumab
Imatinib
mesylate
(Gleevec),
sunitinib
carfilzomib
(Kyprolis),
lenaliomide
tube/primary
peritoneal
cancers:
Bevacizumab
vandetanib
(Caprelsa),
sorafenib
CONCLUSIONS
Delivery of drug molecule to reach its specific site is itself a difficult task in the complex
cellular network of an organism. Finally, targeted drug delivery is coming forward as one
of the brightest advanced technique in the medical sciences in the diagnosis and
treatment of couple of lethal diseases, specially cancer. It has crossed the infancy period and
now touching height of growths in research and development in clinical and
pharmaceutical fields. 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
and
intelligent
with
time
and
Manifestation of all these strategies and advanced technologies in clinical field leads to new
era of therapeutic and diagnostics in future. New strategies under investigation should
periodically undergo evaluation, taking advantage of the bench to bed-side experience
available today.
REFERENCES: