Basic Overview of Targeted Drug Delivery Systems

1. TARGETED DRUG DELIVERY SYSTEM
Hitesh Udar
M.Pharmacy
PDM University
Department of Pharmaceutics

2. CONTENTS
INTRODUCTION
NEED FOR TDDS
IDEAL CHARACTERISTICS
ADVANTAGES
DISADVANTAGES
CARRIER OR MARKERS
STRATEGIES OF DRUG TARGETING

3. Introduction
 Targeted drug delivery system is a special form of drug
delivery system where the Selective and Effective
Localization of drug into the target at therapeutic
concentrations with limited access to non target sites takes
place.
 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.

4.  Goal:-
 To provide prolong, localized, target and protected drug
interaction with the diseased tissue.
 To achieve a desired pharmacological response at a
selected site without undesirable interaction at other
sites, there by the drug have a specific action with
minimum side effects & better therapeutic index.
 The drugs can be targeted to
 An organ
 Particular tissue or cell
 Intracellular sites
 Virus or bacterial cells

5. Need For TDDS
Pharmaceutical
Reason
• Drug
Instability
• Low
Solubility
Pharmacokinetic
Reason
• Poor
Absorption
• Short Half
Life
• Large
Volume of
Distribution
Pharmacodynamic
Reason
• Low
Specificity
• Low
Therapeutic
Index

6. Ideal Characteristics
 It should be
 Non-toxic
 Biocompatible
 Biodegradable
 Physicochemical stable both in-vivo & in-vitro
 Restricted drug distribution to target cells or tissues or
organs and should have uniform distribution.
 Controlled and predictable drug release.
 Minimal drug leakage.
 Carrier should be readily eliminated without causing any
change in the diseased state.
 Preparation should be easy, reproductive and cost
effective.
 Drug release should not effect drug action.

7. Advantages & Disadvantages
Advantages
 Reduction of Drug side
effects
 Reduced frequency of
drug intake
 Reduced dose of drug
 Uniform blood level of
drugs
 Maximizes the therapeutic
index
 Avoidance of hepatic first
pass metabolism
Disadvantages
 Rapid clearance of targeted
systems.
 Immune reactions against
carrier systems.
 Insufficient localization of
targeted systems in tumor
cells.
 Diffusion and redistribution
of released drug.
 Difficult to maintain stability
of dosage form.
 High cost.

8. Carrier and Markers
 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.
 Carrier is one of the special molecule or system
essentially required for effective transportation of loaded
drug up to the pre selected sites.
 Pharmaceutical carriers :
 Polymers
 Microcapsules
 Microparticles
 Lipoproteins
 Liposomes
 Micelles

9. Strategies of Drug Targeting
Drug
Targeting
Strategies
Passive
Targeting
Inverse
Targeting
Active
Targeting
Ligand
Mediated
Targeting
Physical
Targeting
Dual
Targeting
Double
Targeting
Combination
Targeting

10. 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 responseto physicochemical
characteristics of the drug or drug carrier system.
 Example: uptake of some colloids by RES especially in
liver or spleen => ideal substrate for passive hepatic
targeting of drug

11. Inverse Targeting
 In this type of targeting attempts are made to avoid
passive uptake of colloidal carrier by RES (Reticulo
Endothelial Systems) and hence the process is referred
to as inverse targeting.
 To achieve inverse targeting, RES normal function is
suppressed by pre injecting large amount of blank
colloidal carriers or macromolecules like dextran
sulphate.
 This approach leads to saturation of RES and suppression
of defense mechanism. This type of targeting is an
effective approach to target drug(s) to non-RES organs.
 Example: pre-injection of large amount of blank
colloidal carriers or macromolecules like dextran to
saturate the RES system => drug targeting to NON-RES
ORGANS

12. Active Targeting
 In this approach carrier system bearing drug reaches to
specific site on the basis of modification made on its surface
rather than natural uptake by RES.
 Surface modification technique include coating of surface
with either a bioadhesive, nonionic surfactant or specific cell
or tissue antibodies (i.e. monoclonal antibodies) or by
albumin protein.
 FIRST ORDER: distribution to the capillary bed of target site
like lymphatic, cerebral ventricles etc
 SECOND ORDER: delivery to special cells like tumor or kupffer
cells in liver.
 THIRD ORDER: intracellular localization of dug carrier
complex via endocytosis or ligand mediated entry where
lysosomal degradation of carrier complex causes release of
drug.

13. Ligand Mediated Targeting
 Achieved using specific mechanisms such as receptor
dependent uptake of natural LDL particles and
synthetic lipid microemulsions of partially
reconstituted LDL particles coated with the
apoproteins.
Physical Targeting
 In this type of targeting some characteristics of
environment changes like pH, temperature, light intensity,
electric field, ionic strength small and even specific stimuli
like glucose concentration are used to localize the drug
carrier to predetermined site.
 This approach was found exceptional for tumour targeting
as well as cytosolic delivery of entrapped drug or genetic
material.

14. Dual Targeting
 In this targeting approach carrier molecule itself
havetheir 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.

15. Double Targeting
 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.

16. Combination Targeting
 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 proteins and peptides with natural
polymers such as polysaccharides, or synthetic polymers
such as poly(ethylene glycol) may alter their physical
characteristics and favour targeting the specific
compartment, organs or their tissues within their
vasculature.
 Further vectorization of these modified proteins and
peptides into vesicular or microparticulate carriers may
take advantage of the intrinsic and inherited properties
of carrier to achieve a site specific active targeting of
encapsulated contents.

17. Problems Associated with TDDS
 Rapid clearance of targeted systems specially antibody
targeted carriers.
 Immune reactions against intravenous administered
carrier systems.
 Target tissue heterogeneity.
 Problems of insufficient localization of targeted systems
into tumour cells.
 Down regulation and sloughing of surface epitopes.
 Diffusion and redistribution of released drug leading to
non-specific accumulation.

18. Thank You