NDDS Topics: Targeted drug delivery system

1. TARGETED DRUG DELIVERY
SYSTEM
Prof. Shashank Chaurasiya
Asst. Professor
Bansal College of Pharmacy, Bhopal

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

3. • 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.

5. • Reduction of drug side-effects
• Reduced frequency of drug
intake
• Reduced dose of drug
• Uniform blood level of drug
• Maximizes the therapeutic
index
ADVANTAGES 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. • 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. 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

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

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

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

15. • 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. 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. 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. • 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

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

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

22. 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. 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
Microballons
sol=agitate at 40C =>
microbeads dried
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

25. • 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. • 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. NANO-
CARRI
ER
DESCRIPTIO
N
IMAGE APPLICATIO
N
NANO
SHELLS
Hollow silica
spheres
covered with
gold
Targeting
tumor cells
NANO Metallic:Au,Ni Detect tumor in
WIRES Semi
conducting:Si,
InP
brain,treatment
of Parkinson's
Insulating:SiO2

28. QUANTA
M DOTS
Miniscule
semiconduct
or particles
Targeting
cancerous
cells
GOLD
NANOPARTI
CL ES
Ultra sensitive
detection
system for
DNA& proteins
Genetic
engineerin
g
DENDRIMER
S
Synthetic
nanoparticle
,510nm diameter
Medical
imaging,
gene
transfectio
n

29. • 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

31. 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

32. THANK YOU…