This document discusses targeted drug delivery systems. It begins by introducing the concept of targeted drug delivery as proposed by Paul Ehrlich in 1902 to deliver "magic bullets" of medicine exclusively to target cells. It then outlines several approaches to targeted drug delivery including controlling drug distribution, altering the drug's structure, and controlling drug input for a programmed bio-distribution. Finally, it describes various carrier systems that can be used for targeted drug delivery like liposomes, nanoparticles, antibodies, and ligands to actively target drugs to specific sites.

1. TARGETED DRUG DELIVERY
SYSTEM
By-
Jyotsana

2. CONTENT -
• Introduction
• Concept of drug targeting
• Common approaches for drug targeting
• Ideal properties of targeted drug delivery system
• Advantages and disadvantages of drug targeting
• Mode of drug targeting
• Carrier systems for drug targeting

3. INTRODUCTION
The therapeutic response of a drug depends upon the interaction of drug
molecules with cell on cell membrane related biological events at receptor sites
in concentration dependent manner.
It is apparent that most of disease treated by cytotoxic agents not only demand
for controlled drug delivery but also the pattern of delivery is directed to be
specified, precise and defined at quantitative level.
Therefore, there was a need of developing such a system to overcome the
limitations related to the conventional dosage form and improve the therapeutic
efficacy of drug.

4. CONCEPT OF DRUG TARGETING
The concept of designing targeted drug delivery system (TDDS) was first given
by Paul Ehrlich in 1902.
He proposed the drug delivery to be a “magic bullet” and described TDDS as
an event, where a drug –carrier complex delivers a drug exclusively to the
preselected target cells in a specified manner.
“Targeted drug delivery implies for selective and effective localization of
pharmacologically active moiety at preselected targets in therapeutic
concentration, while restricting its access to non-target normal cellular linings,
thus minimizing toxic effects and maximizing therapeutic index”.

6. Need of
Targeted Drug
Delivery
System
Pharmaceutical
Reason
Low solubility
Drug instability
Pharmacodynamic
Reason
Low specificity
Low therapeutic
index
Pharmacokinetic
Reason
Poor absorption
Short half-life
Large Volume of
Distribution

7. APPROACHES FOR DRUG TARGETING
Controlling the distribution of drug by incorporating it in a carrier
Altering the structure of the drug at molecular level
By controlling the input of the drug into the bio-environment to ensure a
programmed and desired bio-distribution.

8. IDEAL PROPERTIES OF TDDS
 Nontoxic, biocompatible and physiochemical stable in-vivo and in-vitro.
Restrict drug distribution to target cells or tissue or organ.
Controllable and predictable rate of drug release.
Minimal drug leakage during transit.
Carrier used must be biodegradable or readily eliminated from the body without
any problem.
Its preparation should be easy or reasonably simple, reproductive and cost
effective.

9. DRUG TARGETING
Advantages
 Reduced toxicity.
 Bypass hepatic first pass
metabolism.
Reduced dose and dosing intervals.
No peak and valley plasma
concentration.
Enhancement of the absorption of
target molecules such as peptides
and particulates.
Disadvantages
 Rapid clearance of targeted
system.
Immune reactions against i.v
administered carrier system.
Diffusion and redistribution of
released drug.
Drug deposition at the target site
may produce toxicity symptoms.
Difficult to maintain stability of
dosage form.

10. Drug
Targeting
Strategies
Passive
targeting
Active
targeting
Inverse
targeting
Dual
targeting
Double
targeting
Combination
targeting

11. PASSIVE TARGETING
In Passive targeting, we make use of and modify the physiochemical properties of
the drug carrier complex, so that it escapes body defence system and accumulate
in the target tissue.
Passive process utilises the natural course of bio distribution of the carrier system,
through which it eventually accumulate into the organ compartment of body.
It refers to the system that targets the systemic circulation i.e., targeting occurs
because of body’s natural response to the physiochemical characteristic of the drug
or drug-carrier system.

12. Few examples of passive targeting
The colloids which are taken up by the reticulo-endothelial system (RES)
can be ideal vector for passive targeting of drugs to RES predominant
compartments.
In case of cancer treatment the drug carrier complex can be targeted to
the tumour site by employing the Enhanced permeability retention
(EPS) effect.
Passive targeting may also be directed to lymphoid organs, as these organs
are finely structured and nanoparticles may easily penetrate into lymphatic
vessels.

14. INVERSE TARGETING
It is based on avoiding passive uptake of colloidal carriers by RES. In other
words, it is reversion of bio distribution trend of the carrier.
It can be achieved by supressing the function of RES by pre-injection of a large
amount of blank colloidal carriers or macromolecules like dextran sulphate.
Alternative strategies include modification of size, surface charges, composition,
surface rigidity & hydrophilicity characteristics of carriers for desirable biofate.
For example- In 1985, Hansrami, reported that phospholipid microsphere
emulsified with polaxmer 338 (hydrophillic non-ionic surfactant) showed the
lowest RES uptake.

15. ACTIVE TARGETING
This type of targeting exploits modification or manipulation of drug carrier to
redefine its bio-fate. Natural distribution pattern of the drug carrier composites is
enhanced using the chemical, biological and physical means.
The ease of the binding of the drug-carrier to target cells through the use of ligands
or engineered homing devices (antibodies, peptides, sugar &vitamins) to increase
localization of the drug and target specific delivery of drug is referred to as active
targeting.
There are three levels of active targeting – first order (organ compartmentalization),
second order (cellular targeting) and third order (intracellular targeting).

16. • Restricted distribution of drug carrier system to the capillary bed
of a predetermined target site, organ.
• Ex- Compartmental targeting in lymphatic, peritoneal cavity,
plural cavity, cerebral ventricles etc.
First
Order
• When the drug delivery system releases the drug into a particular
cell within an organ or tissue, it is called cellular targeting.
• Ex- Selective drug delivery to kuppfer cells in the liver.
Second
order
• When the delivery system can enter specific cells and leave the
drug intracellular, then it is called third order or sub cellular
targeting process.
• Ex- Receptor based ligand mediated entry of a drug complex into
a cell by endocytosis.
Third
order

17. Ligand mediated active targeting
A ligand (homing device) is some molecule which we attach to the drug
delivery system and takes it to the target site. A ligand and its receptor form a
complex because structurally they are complimentary to each other.
A variety of molecules are represented as ligands including antibodies,
hormones, low density lipoproteins etc.
Example- Biotin avidin conjugates

18. Biotin avidin conjugates

19. PHYSICAL TARGETING
The selective drug delivery programmed and monitored at the external level
(ex-vivo) with the help of physical means is referred to as physical targeting.
In this mode of targeting, some characteristics of the bioenvironment are used
either to direct the carrier to a particular location or to cause selective release of
its content.
Ex.- Temperature sensitive liposomes and acid swelling chitosan nanoparticles.

20. PHYSICAL TARGETING
Physical targeting Formulation system Mechanism for drug delivery
Heat Liposome Change in permeability
Magnetic modulation Magnetically responsive microspheres
containing iron oxide
Magnetic flow can retard fluid flow of
particles
Ultrasound Polymers Change in permeability
Electrical pulse Gels Change in permeability

21. DUAL TARGETING
This approach employs carrier molecules which have their own intrinsic
antiviral effect thus synergies the antiviral effect of the loaded active drug.
Major advantage of the dual targeting is - virus replication process can be
attacked at multiple points, excluding the possibilities of resistant viral stain
development.

22. DOUBLE TARGETING
Spatial
control
Temporal
control
Double
Targeting
Targeting drugs to
specific organs,
tissues, cells or
even sub cellular
compartment
Controlling the
rate of drug
delivery to target
site.

23. COMBINATION TARGETING
The idea of combination targeting was proposed in 1998, by Petit and Gombtz.
It can be given as site specific targeting for delivery of protein and peptides.
These targeting systems are equipped with carriers, polymers and homing devices
of molecular specificity that could provide a direct approach to target site.
Modification of polymer with natural polymers may alter their physical
characteristics and favour targeting the specific compartments, organs or tissue
within the vasculature.

24. COMPONENTS OF DRUG TARGETING
Target • Specific organ or a cell or a group of cells, which in
chronic or acute condition need treatment
Carrier
• Special molecules or system essentially required for
effective transportation of loaded drug up to the pre
selected sites.

25. Different Carriersused in drug targeting