NDDS 7th SEMESTER UNIT 4

1. TARGETED
DRUG
DELIVERY
SYSTEMS

2. INTRODUCTION
 Drug delivery to the body can be divided into two broad groups: (I) Local (II) systemic.
 The local delivery of drugs is available only for the external sites of the body while drug delivery to
internal sites of the body is usually systemic.
 In case of systemic delivery drugs are sent into systemic circulation in a therapeutic concentration
range, which besides reaching the decreased site reach the majority of other sites of the body.
 This exposure of the drug to the other sites of the body causes various side-effects and
maintenance of therapeutic concentration requires a large dose of the drug.
 One more problem is maintenance of steady drug concentration for a longer period of time, which
is faced in the treatment of chronic diseases.
 Multiple dosing usually leads to the drug concentration falling off the therapeutic range many
times.
 Because of these problems associated with the conventional systemic delivery of the drugs there
is a need for the development of a targeted drug delivery system - a system that can deliver the
drug selectively to the diseased site in a specified steady concentration for the prescribed time.

3. TARGETED DRUG DELIVERY SYSTEMS
 Targeted drug delivery, sometimes called smart 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.

4.  “TDDS (smart delivery system) means selective and effective localization of the pharmacologically active
moiety at pre identified target(s) in therapeutic concentration, while restricting its access to non targets,
thus minimizing its toxic effects and maximizing its Therapeutic index”.
OR
 “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 the capillary bed of the active sites.
• To the specific type of cell (or) even an intracellular region.
Ex: Tumour cells but not to normal cells.
• To a specific organ (or) tissues by complexion with the carrier that recognizes the target.
CONTD…

5. IDEAL CHARACTERISTICS
 Restrict drug distribution to target cells
or tissues or organs and should have
uniform capillary distribution.
 Controllable and predictive rate of drug
release.
 Drug release does not effect the drug
action.
 It should be nontoxic, biocompatible,
biodegradable, and physiochemically
stable both in vivo and in vitro.
 Therapeutic amount of drug release.
 Minimal drug leakage during transit.
 Carriers used must be bio-degradable
or readily eliminated from the body
without any problem and no carrier
induced modulation of diseased state.
 The preparation of the delivery system
should be easy or reasonably simple,
reproductive and cost effective.

6. ADVANTAGES
 Target drug delivery system reduces the
side effects and toxicity.
 The Dose of the drug reduces by
targeting organ.
 It avoids the degradation of drug (first
pass metabolism).
 Drug bioavailability increases and
fluctuation in concentration decreases.
 It also has positive effect on permeability
of proteins and peptide.
 These all factors in combination cause in
reduction in dosage frequency and hence
reduce the cost of expensive drug.
DISADVANTAGES
 With the targeted drug delivery it
becomes difficult (not impossible) to
target the tumor cells.
 Advanced techniques and skilled
persons are required.
 Sometimes it may causes toxicity and
it is very difficult to maintain stability
of dosage forms.

7. TYPES OF TARGETED DRUG DELIVERY
Types of
Targeted
Drug
Delivery
Active
Targeting
Passive
Targeting
Inverse
Targeting
Dual
Targeting
Double
Targeting
Combination
Targeting

8. ACTIVE TARGETING
 Active targeting means a specific ligand– receptor type interaction for intracellular localization which occurs
only after bloodcirculation and extravasations.
 This active targeting approach can be further classified into three different levels of targeting which are
1. First order targeting refers to restricted distribution of the drug carrier systems to the capillary bed of a
predetermined target site, organ or tissue e.g. compartmental targeting in lymphatics, peritoneal cavity, plural
cavity, cerebral ventricles and eyes, joints.
2. Second order targeting refers to selective delivery of drugs to specific cell types such as tumour cells and not
to the normal cells e.g. selective drug delivery to kupffer cells in the liver.
3. Third order targeting refers to drug delivery specifically to the intracellular site of targeted cells e.g. receptor
based ligand mediated entry of a drug complex into a cell by endocytosis

9. PASSIVE TARGETING
 Drug delivery systems which are targeted to systemic circulation are
characterized as Passive delivery systems.
 In this technique drug targeting occurs because of the body’s natural
response to physicochemical characteristics of the drug or drug carrier
system.
 The ability of some colloid to be taken up by the Reticulo Endothelial Systems
(RES) especially in liver and spleen made them ideal substrate for passive
hepatic targeting of drugs

10. INVERSE TARGETING
 This approach leads to saturation of RES and suppression of defense mechanism.
 This type of targeting is a effective approach to target drug(s) to non-RES organs.
 In this targeting approach carrier molecule itself have 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.
DUAL TARGETING

11. DOUBLE TARGETING
 When temporal and spatial methodologies are combined to target a carrier system, 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.
COMBINATION TARGETING
 These targeting systems are equipped with cariers, polymers and homing devices of
molecular specificity that could provide a direct approach to target site.

12. LIPOSOMES
 Derived from two Greek words: 'Lipos'
meaning FAT and 'Soma' meaning
BODY.
 Concentric bilayered vesicles in which
an aqueous core is entirely enclosed
by a membranous lipid bilayer mainly
composed of natural or synthetic
phospholipids.
 The structural components of liposomes
include:
 a. Phospholipids
 b. Cholesterol

13. THERAPEUTIC APPLICATIONS
Anticancer Therapy: Toxicities can be reduced by 50% by using encapsulated liposomal preparations but
the efficiency may be compromised due to bioavailability variations in some cases.
Ocular Drug Delivery: Enhance penetration of drug in eye.
Pulmonary Drug Delivery: Good solubilization capacity of liposomes make them a useful tool for the
delivery of drug through this route.
Topical Drug Delivery: Enhance skin permeability and also increase Drug transport due to the
lipophilicity of the vesicles.

14. NIOSOMES
 Niosomes are ampiphillic , non-ionic surfactant vesicles.
 It hold hydrophilic drugs within the core or space enclosed in the vesicle, while
hydrophobic drugs are embedded within the bilayer itself.
 The first niosome formulations were developed and patented by L’Oreal in 1975
 Niosomes can entrap solutes.
 Niosomes are osmotically active and stable. Accommodate the drug molecules with a
wide range of solubility.
 Exhibits flexibility in their structural characteristics (composition, fluidity and size)
 Performance of the drug molecules is increased.
 Better availability to the particular site by protecting the drug from biological
environment.
 Surfactants used in preparation are biodegradable, biocompatible and non-immunogenic.

15. APPLICATION OF NIOSOMES
Niosome as a
carrier for Hb
Ophthalmic drug
delivery
Delivery of
peptide drugs
Neoplasia
Use in studying
immune
response
Anti-
inflammatory
agents
Niosomes in gene
delivery

16. MONOCLONAL ANTIBODIES
 An antibody is a protein used by the immune system to identify and neutralize foreign objects like
bacteria and viruses.
 Each antibody recognizes a specific antigen unique to its target.
 Monoclonal antibodies (mAb) are antibodies that are identical because they were produced by one
type of immune cell, all clones of a single parent cell.
 The specificity of the toxins is increased by using MAbs as active drug targeting systems.
 Drug immunoconjugates: Agents like chlorambucil, methotrexate and doxorubicin are conjugated with
tumor specific antibodies. Ex: doxorubicin-BR96 immunoconjugate for Lewis antigen found on the
surface of tumor cells.
 Uses for monoclonal antibodies include:
Cancer, Rheumatoid arthritis, Multiple sclerosis, Cardiovascular disease, Systemic
lupus erythematosus, Crohn's disease, Ulcerative colitis, Psoriasis.

17. ADVANTAGES & LIMITATIONS OF MONOCLONAL
ANTIBODIES
Limitations
1. As they are specific to a particular antigen, they
cannot distinguish molecule as a whole.
2. Some times they cannot distinguish groups of
different molecules. Ex:- presence of retro viruses
as a part of mammalian chromosomes is not
distinguished.
3. The presence of some of these viruses is detected
in hybridomas. This poses a great danger since
there is no guarantee for MAb produced is totally
virus free.
4. For this reason US food and drug administration
insists that MAb for human use should be totally
free from all pathogenic organisms including
viruses.
Advantages
1. They are homogenous in nature.
2. They are specific to a particular antigen with a
particular epitope.
3. Ex:Rituximab (Rituxan®, anti-CD20) is a good
example – this antibody is used for the treatment
of lymphoma.
4. Monoclonal Antibodies Approved By FDA
Antibody Target Indication Trastuzumab HER2
Breast Cancer Bevacizumab VEGF Lung Cancer
Cetuximab EGFR Colorectal carcinoma
Panitumumab EGFR Colorectal carcinoma

18. NANOPARTICLES
 “ Nanoparticles are nanosized colloidal structures composed of synthetic or semi- synthetic polymers.”
Size range : 10–1000 nm
 The drug is dissolved, entrapped, encapsulated or attached to a nanoparticle matrix.
 The first reported nanoparticles were based on non-biodegradable polymeric system that is
polyacrylamide, polymethyl methacrylate, polysterene etc. by Birrenbach and Speiser , 1976 ; Kreuter and
Speiser , 1976.
 ADVANTAGES
1. Nanoparticles can act as controlled release system depending on their polymeric composition.
2. Less amount of dose required.
3. They enhance aqueous solubility of poorly soluble drug therefore increase its bioavailability, therapeutic
efficacy and Reduces side effects.
4. Nanoparticles can be administer by various routes including oral, nasal, parenteral, intra-ocular etc.
5. As a targeted drug carrier nanoparticles reduce drug toxicity.

19. NANOPARTICLES APPLICATIONS
 Targeted drug delivery
 Alternative drug and vaccine delivery mechanisms (e.g. inhalation, oral in place of injection).
 Bone growth promoters
 Cancer treatments
 Biocompatible coatings for implants
 Sunscreens (e.g. using ZnO and TiO2) / cosmetics
 Bio labeling and detection (e.g. using Au)
 Carriers for drugs with low water solubility