2. S. No. CONTENTS
1. INTRODUCTION
2. DIFFERENCE BETWEEN : TARGETED & CONVENTIONAL
DRUG DELIVERYSYSTEM
3. DRUG TARGETING STRATEGIES
4. CARRIER CONCEPTS IN DRUG DELIVERY
5. SITE-SPECIFIC DRUG DELIVERY
6. MARKETED PREPARATIONS
7. CURRENT MARKET SALES DATAOF TDDS
8. CONCLUSION
9. REFERENCES
3. Targeted drug delivery means accumulation of pharmacologically active
moiety at desired target in therapeutic concentration at the same
restricting its access to normal cellular lining, thus minimizing
therapeutic index. The drug can be targeted to intracellular sites, virus
cells, bacteria cell and parasites using different scientific strategies have
proven highly effective.[1]
HISTORY
The concept of targeted drugs is not new, but dates back to 1906
when Ehrlich first postulated the âmagic bulletâ. The durability of
this concept is a strong indication of its appeal, but the âmagic
bulletâ continues to be a challenge to implement in the clinic.
4. Sr.
no.
Targeted Drug Delivery System Conventional Drug Delivery
System
1. Specific Location Equally distributed
2. High efficacy Lower efficacy
3. Less side effects More side effects
4. Low frequency High frequency
5. Low fluctuation in circulating
drug levels
High fluctuation in circulating
drug levels
DIFFERENCE BETWEEN : TARGETED &
CONVENTIONAL DRUG DELIVERY SYSTEM
6. 1. Passive Targeting :-
Drug delivery systems which are
targeted to systemic circulation are
characterized as Passive delivery
systems. The ability of some colloid to
be taken up by the Reticulo Endothelial
Systems (RES) especially in liver and
spleen make them ideal substrate for
passive hepatic targeting of drugs.
2.Inverse Targeting:-
In this type of targeting attempts are
made to avoid passive uptake of
colloidal carrier by RES and hence the
process is referred to as inverse
targeting.
7. 3. Active Targeting :-
In this approach carrier system bearing
drug, reaches to specific site on the basis
of modification such as coating of
surface with either a bioadhesive,
nonionic surfactant or specific cell or
tissue antibodies (i.e. monoclonal
antibodies) or by albumin protein are
made on its surface rather than natural
uptake by RES
4. Ligand-mediated Targeting :-
Ligand-targeted nanoparticles bind
selectively to target cells, such as tumor
cells.
8. 5. Physical Targeting :-
The external triggers can be employed both
with and without active targeting. In the
case of only external triggers being used,
then the targeting strategy is known as
âphysical targetingâ. The commonly
employed external triggers are ultrasound,
magnetic field, electric field and infrared
radiation.
6.Dual Targeting :-
In this targeting approach carrier molecule
itself have their 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.
9. 7. Double Targeting :-
The combination is made between spatial control & temperature controlled drug
delivery ,when these two methodologies are combined, it is called as Double
targeting.
10. 8. Combination Targeting :-
The use of both external triggers and active targeting is known as âcombined
targetingâ. External triggers can also be used along with passive targetingand
forms a subset of combined targeting.
12. 1.LIPOSOMES
Liposomes were first described by
Bangham in 1965. The name
liposome is derived from two Greek
words: 'Lipos' meaning fat and 'Somaâ
meaning body.
Mechanisms of Liposomes:
1. Liposome attaches to cellular
membrane and appears to fuse with
them, releasing their content into
the cell.
2. They are taken up by the cell and
their phospholipids are incorporated
into the cell membrane by which
the drug trapped inside is released
3. In case of
Liposomes
phagocyte
are taken
cell, the
up, the
phospholipid walls are acted upon
by organelles called lysosomes and
the active pharmaceutical
ingredients are released.
13. APPLICATION OF LIPOSOMES IN PHARMACEUTICALINDUSTRY
Sr.
No.
Liposome
Utility
Examples Disease States
Treated
1. Sustained-
Release
Systemic antineoplastic drugs,
hormones, corticosteroids, drug
depot in the lungs
Cancer, bio
therapeutics
2. RES Targeting Immuno modulators, vaccines,
antimalarials, macrophage-located
diseases
Cancer, MAI, tropical
parasites
3. Site-Avoidance Amphotericin B â reduced
nephrotoxicity, doxorubicin â
decreased cardiotoxicity
Fungal infections,
cancer
4. Drug protection Cytosine arabinoside, interleukins Cancer
5. Specific
Targeting
Cells bearing specific antigens Wide therapeutic
applicability
15. 2.NIOSOMES
A Niosome
ionic surfactant-based
formed mostly
is a non-
Vesicle
by
nonionic surfactant and
an excipient. They
cholesterol incorporation as
are
structurally similar to liposomes
in having a bilayer, however,
they are more stable than
liposomes.
17. 3.SUBMICRON EMULSIONS
Submicron emulsion can be defined as emulsions with mean droplet diameters
ranging from 50 to1000 nm. Usually, the average droplet size is between 100
and 500 nm. The globules can exist as water-in-oil and oil-in-water forms,where
the core of particle is either water or oil, respectively.
Limitation of submicron emulsion
The main limitation of submicron emulsion is use of high amount of surfactant
and cosurfactant that may be harmful for human consumption.
19. 4.MULTIPLE EMULSIONS
Multiple emulsions are the emulsion systems in which the dispersed phase
contains smaller droplets that have the same composition as the externalphase.
This is made possible by âDouble Emulsificationâ.
There are 2 types of Multiple Emulsions :
MULTIPLE
EMULSIONS
Oil-in-water-in-
oil (O/W/O)
emulsion
system
Water-in-oil-in-
water (W/O/W)
emulsion
system
22. Polysaccharides
ProteinsSynthetic
polymers
Rolland et. al., (1989) designed a site specific drug delivery
system consisting of polymetacryclic nanoparticles. The main
goal in designing nanoparticles as a delivery system are to
control size of particle, surface characteristics and discharge of
pharmacologically active agents in order to achieve the site
specific action of the drug at the therapeutically optimal rate and
dose regimen.
Preparation
PARTICLE SIZE
1.Ultrafine particles -1 and 100 nm in size.
2.Fine particles -100 and 2,500 nm.
3.Coarse particles -2,500 and 10,000 nm.
24. APPLICATIONS
Cancer therapy
MATERIAL PURPOSE
Poly (alkyl cyanoacrylate) Targeting, reducing toxicity, enhanced
nanoparticles with anti cancer agents, uptake of anti tumour agents, oligo
nucleotides improved invitro and invivo stability
Intracellular targeting Poly (alkyl cyanoacrylate) polyester Target reticuloendothelial intercellular
nanoparticles with anti parasitic or infections
Prolonged systemic circulation
anti viral agents
Poly esters with adsorbed
ethylene glycols or pluronics
poly Prolonged systemic drug effect, avoid
uptake by the reticuloendothelial
system
Vaccine adjuvant Poly (methyl methacrylate) Enhanced immune response alternate
nanoparticles with vaccines (oral and acceptable adjuvant
Peroral absorption
IM immunization)
Poly (methyl
nanoparticles with
therapeutic agents
protectionmethacrylate) Enhanced bioavailability
proteins and from GIT enzymes
25. Ocular delivery Poly (methyl
nanoparticles with
inflammatory agents, anti-bacterial
agents for glaucoma
methacrylate) Improved retention of drug/
steroids , anti- reduced wash out
Oligonuleotide delivery ofAlginate nanoparticles , poly (D,L â Enhanced delivery
lactic acid) nanoparticles oligonucleotides
DNAdelivery DNA- gelatin nanoparticles, DNA- Enhanced delivery and
chitosin nanoparticles significantly higher expression
levels
Other applications Poly (alkyl cyanoacrylate) Crosses blood-brain
nanoparticles with peptides Poly (alkyl immunoassays,
barrier,
improved
cyanoacrylate) nanoparticles, absorption and permeation for
nanoparticles with adsorbed enzymes, transdermal applications,
nanoparticles with radioactive or enzyme immunoassays, radio
contrast, copolymerized peptide imaging agents, oral delivery of
nanoparticles of activated peptides peptides
26. 6.RESEALED
ERYTHROCYTES
Erythrocytes, the most abundant cells in
the human body, have potential carrier
capabilities for the delivery of drugs.
Erythrocytes
biodegradable,
are biocompatible,
possess very long
circulation half lives and can be loaded
with a variety of chemically
biologically active compounds
and
using
various chemical and physical methods.
Application of erythrocytes as
promising slow drug release or site-
targeted delivery systems for a variety
of bioactive agents from different fields
of therapy has gained a remarkable
degree of interest in recent years.
29. 7.MICROSPHERE
SMicrospheres as carriers of drug become an approach of controlled release
dosage form in novel drug delivery system. Microspheres are sometimes
referred to as microparticles. Microspheres can be prepared from variousnatural
and synthetic materials. Polymer microspheres, Glass microspheres and ceramic
microspheres are commercially available.[1]
Common types of polymer microspheres :-
1.Polyethylene microspheres
2. Polystyrene microspheres
31. 8.MAGNETICALLY MODULATED DRUG DELIVERY
Magnetic drug delivery is a novel approach to deliver drug using
engineered âsmartâ micro carriers which appears to overcome a
number of limitations facing current methods of delivering
medicines.
ď Principle of Magnetism for micro particles
Magnetic carriers are normally grouped according to size.
At the lower end, we have the ferrofluids,
ď which are colloidal iron oxide solutions. Encapsulated
magnetite particles in the range of 10â500 nm are usually
called magnetic nanospheres and any Magnetic particles of
just below 1â100Âľm are magnetic microspheres. In general,
magnetic liposomes are also included when speaking about
magnetic carriers
32. Mechanism
1.The release of macromolecules from EVAc systems without magnetic beads,
suggests that molecules with molecular weight greater than 300 cannot
permeate the polymer.
2.The direct incorporation of macromolecules in the polymer-macromolecule
using cast procedure caused a tortuous and complex series of pores formation
within the matrix.
3.The release rates are determined by factors affecting permeation of water into
the polymer and drug out of these pores.
Applications
of MMDD
Contraceptive
Drug
Delivery
Infusion
PumpsImplants
36. Rate-limiting role of the BBB in brain drug development :
BBB have efficient ability to restrict and separate the human brain from
circulatory network & also limits the transport of water and lipidsoluble
substances from blood circulation into CNS.
37. Osmotic &
Chemical
opening of BBB
By passing the
BBB
Direct invasive
methods
Various
pharmacological
agents to unblock
the BBB
Strategies utilized
to manipulate
BBB to target
brain
44. The transdermal drug delivery system is a therapeutic system designed to
transfer drugs through intact skin for systemic treatment & it offers controlled
drug release pattern by a simple application to the skin surface, eliminating
the gastrointestinal absorption associated with oral administration and
providing for more efficient drug utilization.
COMPONENTS OF TRANSDERMAL DEVICES
48. Development of effective targeted bone marrow drug delivery systems is an
important goal for development of diagnostic, protective, and therapeutic
agents for hematopoietic disorders and infectious diseases in which
colonizing pathogens are difficult to eradicate.
DISEASES
CURED
Aplastic
Anaemia
Hodgkinâs
disease
Leukaemia
Multiple
Myeloma
Thalassemia
Peripheral
stem cell
transplants
51. To achieve successful colonic delivery, a drug needs to be
protected from absorption and /or the environment of the upper
gastrointestinal tract (GIT) and then be abruptly released into the
proximal colon, which is considered the optimum site for colon-
targeted delivery of drugs.
59. Vaginal drug delivery system offers an avenue for the release of different
antifungal, antibacterial and contraceptive drugs.
Conventional vaginal dosage forms have several benefits like :-
1.Avoid the first pass metabolism
2.Easy to formulate
3.Self administration is possible
4.Economical.
DOSAGE
FORMULATIONS
Controlled/
Sustained
release
vaginal tablets
Vaginal
Nanoparticles
Vaginal
Microspheres
Vaginal
Rings
62. Targeted drug delivery in oncology provides a localized
and prolonged drug delivery to the affected organ or
tissues.The treatment of cancer depends upto the stage to
which the cancer has progressed.
66. Gastroretentive drug delivery is an approach to prolong gastric residence time,
thereby targeting site-specific drug release in the upper gastrointestinal tract
(GIT) for local or systemic effects.
FACTORS
CONTROLLING
GASTRIC
RETENTION
Density of
dosage
forms
Density of
dosage
forms
Food
intake and
its nature
Effect of
gender,
posture
and age
70. Sr.
no.
Name of
preparation :
Manufacturer
Type / Mode of
delivery
Uses Image
1. Depocyt : Pacira
Pharmaceuticals
Liposome
Injection / Oral
delivery
Intrathecal
treatment of
lymphomatous
meningitis.
2. Estrasorb : Graceway
Pharmaceuticals
Topical emulsion
/ Topical delivery
Treatment of
moderate to
severe vasomotor
symptoms due to
menopause
3. Onivyde : Merrimack
Pharmaceuticals
Liposome
injection /
Intravenous
delivery
In combination
with fluorouracil
and leucovorin,
for the treatment
of metastatic
adenocarcinoma
of the pancreas
72. Type Segment Analysis :
1.Nano Tubes
2.Nano Wires
3.Nano Shells
4.Quantum Dots
5.Nano Pros
Applications Segment Analysis :
1.First Order Targeting (Organ Compartmentalization)
2.Second Order Targeting (Cellular Targeting)
3.Third Order Targeting (Intracellular Targeting)
73.
74.
75. The current focus in pharmaceuticals is shifting to a âsmart
drugâ paradigm, in which increased efficacy and decreased
toxicity are the motivating factors.
Rationally designed drug delivery system enables us to precisely
control drug release rates for prolonged duration and sometimes
help targeting the drugs such as anti cancer agents to specific
body sites.
Only in recent years, the idea of development of such systems
became practical. In a short time, targeted drug delivery systems
have had an impact on nearly every branch of medicine.