1. TARGETED DRUG DELIVERY
SYSTEM
SHIPRA MALIK
PHARMACEUTICS

2. CONTENTS
• INTRODUCTION
• NEED OF TDDS
• ADVANTAGES & DISADVANTAGES
• IDEAL TDDS
• CARRIERS
• STRATEGIES
• SYSTEMS
• MICROSPHERES: MAGNETIC MICROSPHERE
• NANOPARTICLES

3. INTRODUCTION
• Targeted drug delivery(Smart Drug Delivery) means selective and effective
localization of drug into the target at therapeutic concentrations with
limited access to non target sites .
• The drug can be targeted to
 an organ
 particular tissue or cell
 intracellular sites
 virus or bacterial cells
GOAL - prolong ,localize, target, and have a protected drug interaction with the
diseased tissue.

4. NEED OF TARGETED DRUG DELIVERY

5. Advantages and Disadvantages
ADVANTAGES
• Reduction of drug side-effects
• Reduced frequency of drug
intake
• Reduced dose of drug
• Uniform blood level of drug
• Maximizes the therapeutic
index
DISADVANTAGES
• Rapid clearance of targeted
systems
• Immune reaction against
carrier systems
• Insufficient localization of
targeted systems in tumor
cells
• Diffusion and redistribution of
released drug
• High cost

6. PROPERTIES OF IDEAL TDDS
• It should be -
o Non-toxic
o Biocompatible
o Biodegradable
o Physicochemical stable both in-vivo & in-vitro
• Controlled and predictable drug release
• Minimal drug leakage
• Carrier should be readily eliminated without causing any change in
diseased state
• Preparation should be easy, reproductive and cost effective
• Drug release should not effect drug action

7. CARRIERS OR MARKERS
Engineered vectors which retain drug inside or onto them to delivery it
within or vicinity of target.
PROPERTIES
• Cross anatomical barriers; tumor vasculature
• Linkage to be stable in biological fluids
• Selectively and specifically recognize target cells

8. STRATEGIES OF DRUG TARGETING

9. Passive or Inverse
PASSIVE
• DDS targets the systemic
circulation of body
• Drug targeting occurs due to
body’s natural response to the
physicochemical properties of
drug or carrier system
• Example: uptake of some colloids
by RES especially in liver or spleen
=> ideal substrate for passive
hepatic targeting of drug
INVERSE
• Uptake of the DDS like colloids by
RES is avoided, hence called
INVERSE TARGETING
• Example: preinjection of large
amount of blank colloidal carriers
or macromolecules like dextran to
saturate the RES system => drug
targeting to NON-RES ORGANS

10. ACTIVE TARGETING
• Carrier system is modified on its surface to deliver drug to a specific
site
• 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.

11. TARGETING STRATEGIES
DUAL TARGETING
• CARRIER MOLECULE also has their own therapeutic activity and thus increases
therapeutic effect of drug
• Net SYNERGISTIC EFFECT of drug conjugate
DOUBLE TARGETING
• TEMPORAL & SPATIAL methodologies are combined in a delivery system
• SPATIAL PLACEMENT : targeting drugs to specific organs, tissues or
subcellular compartments
• TEMOPAL DELIVERY :controlling the rate of drug delivery

12. CARRIER SYSTEMS
• Colloidal carriers
• Cellular carriers
: erythrocytes, platelets, antibodies
• Supramolecular delivery system
:micelles, lipoproteins(VLDL,LDL)
• Polymer based system
• Macromolecular carrier
:MABS, polysaccharides

13. COLLOIDAL CARRIER SYSTEMS
• Vesicular systems
 Liposome
 Virosome
 Pharmacosome
• Microparticulate systems
 Nanoparticles
 Microspheres

14. MICROSPHERES
• Microspheres are small spherical particles,
with diameters in the micrometer range
(typically 1 μm to 1000 μm).
• Also called as -
– Microparticles
– Microbeads

15. MATERIALS USED
• NATURAL POLYMERS
 Proteins: albumin, gelatin, collagen
 Carbohydrates: starch, agarose
 Chemically modified carbohydrates: poly(acryl) dextran, poly(acryl)
starch
• SYNTHETIC POLYMERS
 Biodegradable: lactides & their gylcolides, polyanhydrides
 Non-biodegradable: polymethyl methacrylate,acrolein

16. TYPES OF MICROSPHERE
NATURE DESCRIPTION IMAGE APPLICATION
BIO ADHESIVE •Intimate contact
with absorption site
•Prolonged
residence time
Nasal
:gentamycin,insulin
Ocular:methylpredni
solone
FLOATING
(GRDDS)
•Bulk density less
than gastric fluid
•2 types : hollow
: microballon
NSAIDS,
antibiotics

17. TYPES OF MICROSPHERE
NATURE DESCRIPTION IMAGE APPLICATION
RADIO ACTIVE
MICROSPHERES
Radionuclide tightly
bound to
microbead
Alpha:10cell layer
Beta:Not more than
12mm
Gamma:several cm
Diagnostic(gamma):
spleen,liver imaging
Therapeutic(alpha/
beta):radioemboliza
tion therapy
POLYMERIC
MICROSPHERES
•Biodegradable
•Non-biodegradable
•Swell in aqueous
medium
Vaccine :hepatitis
Local:protein,horm
ones

18. MAGNETIC MICROSPHERE
• Supramolecular particles small enough to circulate through
capillaries without producing embolic occlusion
• But are to be captured in micro vessels
• Dragged into the adjacent tissue by magnetic field of 0.5-0.8 Tesla
• Magnetite(Fe3O4) : ferromagnetic material that is incorporated in
microspheres to make them magnetically responsive

19. TARGETING OF MAGNETIC MICROBEAAD

20. REALEASE OF DRUG
• Freely moves through the capillaries
• Application of external magnetic field result in accumulation of drug
at target site

21. APPLICATIONS OF MAGNETIC MICROBEADS
• Localization of therapeutic agent
• Bioengineering & biomedical trends like enzyme
immobilization, protein purification, cell isolation
• DNA analysis
• Drug discovery
• Molecular targeting

22. PREPARATION OF MICROSPHERES
METHOD DESCRIPTION APPLICATION
Emulsion solvent
evaporation
Drug+polymer sol=>to
aqueous phase(PVP) =
EMULSION(O/W)
=>evaporate solvent =
microsphere
•Aceclofenac
microspheres
•Hollow microspheres
Emulsion cross
linking
Drug=+Gelatin sol=>add drops
to liquid
paraffin=emulsion(W/O)=>MIC
ROBEADS washed with
isopropyl alcohol=>add to
glutaraldehyde sol
Gelatin A
microspheres

23. PREPARATION OF MICROSPHERES
METHOD DESCRIPTION APPLICATION
Co-acervation Drug+Polymer sol=>phase
separation -change in T,pH
-salt or non solvent addition
•Proteins
•Steroids
Emulsion-solvent
diffusion
Drug polymer
mix+ethanol:dichloromethane
(1:1)=>add dropwise to SLS
sol=agitate at 40C =>
microbeads dried
Microballons
Ionic gelation Diclofenac sodium+ sodium
alginate aq sol=>add to Ca2+
& chitosan sol in acetic acid =
microsphere kept for 24 hrs
for internal gellification
Diclofenac sodium=> drug
release at pH6.4-7.2

24. COACERVATION METHOD

25. NANOPARTICLES
• 1-100 nanometer in size
• Also called ULTRAFINE
PARTICLES
• NANOTECHNOLOGY defines particle as a small object that behaves
as a whole unit with respect to its transport and properties

26. PROPERTIES
• High surface area- volume ratio
• Act as bridge between bulk materials and atomic/molecular
structures
• Size dependent properties are observed
• Possess unexpected optical properties as they are small
enough to confine their electrons and produce quantum
effects

27. TYPES OF NANOPARTICLES
NANO-CARRIER
DESCRIPTION IMAGE APPLICATION
NANO
SHELLS
Hollow silica
spheres covered
with gold
Targeting tumor
cells
NANO
WIRES
Metallic:Au,Ni
Semi
conducting:Si, InP
Insulating:SiO2
Detect tumor in
brain,treatment
of Parkinson's

28. TYPES OF NANOPARTICLES
QUANTAM
DOTS
Miniscule
semiconductor
particles
Targeting
cancerous cells
GOLD
NANOPARTICL
ES
Ultra sensitive
detection system
for DNA&
proteins
Genetic
engineering
DENDRIMERS Synthetic
nanoparticle
,510nm diameter
Medical
imaging,
gene
transfection

29. PREPARATION OF NANOPARTICLES
• TOP DOWN
Attrition : broad size distribution (10-1000 nm)
: varied particle shape or geometry
: impurities
• BOTTOMS UP METHODS
o Vapor phase fabrication: pyrolysis
o Liquid phase fabrication: sol gel method

30. Fabrication

31. Marketed drugs
BRAND GENERIC
NAME
INDICATION COMPANY
Tricor® Fenofibrate Hypercholesterol
emia
Abbott
Laboratories
Avinza® Morphine
sulphate
Psycho stimulant Elan nano
systems
Rapamune® Rapamycin immunosuppresa
nt
Elan nano
systems