Targeted drug delivery basics, examples, polymers, conjugated drug delivery, drug conjugates, immunotherapies, biopolymers, nanoparticles, robotics, cancer, treatment, chemotherapy

1. GUIDE:
Dr. PRADEEPNAIK
PRESENTER:
SHARMISTHAPAL

2. CONCEPT OF TARGETEDDRUGDELIVERY

3. 3
Target siteNon target
site
Affinity -
toxicity
No affinity-
low effect
Bio-environmental factors
Target site Non target
site
Inactivation
/Less
therapeutic
effect
More
therapeutic
effect
No affinity-
low effect
Targeted
effect
Drug Drug incarrier

4. The capillary bed of
the active sites..
The specific type
of cell.
An
intracellular
region.
A specific organ (or) tissues
by complexion with the
carrier that recognizes the
target.

5. Ideal Characteristics Of TDDS
Specifically target the drug to
target cells or target tissue
Keep the drug out of non-target
organs, cells or tissue
Ensure minimal drug leakage
during transit to target

8. 8
Components Of Targeted Drug Delivery System
Components Purpose
The active moiety To achieve the therapeutic
effect.
The carrier system
(which can be either soluble or
particulate)
To effect a favorable
distribution of the drug.
To protect the drug from
metabolism.
To protect the drug from
early clearance.
A “homing device” To specifically target the
drug to the target cells or
target tissue.
C

9. Targeted drug delivery can be achieved by
using carrier system.
Carrier is one of the special molecule or system
essentially required for effective transportation of
loaded drug up to the pre-selected sites.
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 OR MARKERS

10. 10
Carrier System Used For Targeted Drug Delivery
Colloidal Carriers Vesicularsystem:
 Liposomes
 Niosomes
 Virosomes
 Immunoliposomes
Microparticulate system:
 Microspheres
 Nanoparticles
Cellular Carriers  Resealed erythrocytes
 Serum albumin
 Antibodies
 Platelets
 Leukocytes
Macromolecular Carriers  Proteins,
 Glycoprotein,
 Neo-glycoprotein
 Polysaccharides

11. Nano Tubes :
They are hollow cylinder made of carbon, atoms which can be
filled and sealed for potential drug delivery.
Application : Cellular scale needle for attaching drug molecule to cancer
cells. As an electrode in thermo cells.

12. Nano shells :
Nano shells are hollow silica spheres covered with gold. Scientists
can attach antibodies to their surfaces, enabling the shells to target
certain shells such as cancer cells. Absorption of light by nanoshells
creates an intense heat that is lethal to cells.
Application : Technique has potential for targeting cancerous drug.

13. Gold Nano:
Particle Scientist uses gold nanoparticle to develop ultrasensitive
detection system for DNA and protein markers associated with many
forms of cancer, including breast, prostrate cancer.
Application : In cancer Treatment and Genetic engineering.

14. Dendrimers :
Dendrimers precisely defined, synthetic nanoparticles that are
approximately 510 nm in diameter. They are made up of layers of
polymer surrounding a control core. The dendrimers surface
contains many different sites to which drugs may be attach.
Dendrimers have a tree-like structure with many branches where a
variety of molecules, including drugs can be attached.
Application : In gene transfection, medical imaging

15. Lipo som es :
Liposomes are simple microscopic vesicles in which an aqueous volume is
entirely composed by membrane of lipid molecule various amphiphelic
molecules have been used to form liposomes. The drug molecules can either
be encapsulated in aqueous space or intercalated into the lipid bilayers The
extent of location of drug will depend upon its physico-chemical characteristics
and composition of lipids.

16. Niosomes:
Niosomes are non ionic surfactant vesicles which can entrap
both hydrophilic and lipophilic drugs either in aqueous phase or in
vesicular membrane made up of lipid materials It is reported to
attain better stability than liposome’s. It may prove very useful
for targeting the drugs for treating cancer, parasitic, viral and
other microbial disease more effectively.

17. Virosomes:
Virosomes are immune modulating liposomes consisting of surface
glycoprotein of influenza virus (immune stimulating
reconstituted influenza virosome) muramyl dipeptide etc.
Virosomes must be target oriented and their fusogenic
characteristics could be exploited in genome grafting and cellular
micro injection.
A. Interaction of the virosomes with
cell surface receptors.
B. Release of the encapsulated drug
molecules in the target cell.

18. Nano robots :
Nano robotics is the technology of creating machines or robots at
or close to the microscopic scale of a nanometre (10−9meters).
More specifically, Nano robotics refers to the still largely
hypothetical nanotechnology engineering discipline of designing
and building

19. Polymer-drug conjugates are
a novel class of nanocairrers
for drug delivery
 protect the drug from
premature degradation,
 prevent drug from
prematurely interaction
with the biological
environment
 enhance the absorption of
the drugs into tissues (by
enhanced permeability and
retention effect or active
targeting).
Polymer drug conjugates system

20. Advantages of Polymer-drug conjugates
An improvement in pharmacokinetics.
Increased water solubility; enhancement of drug
bioavailability.
Protection of drug from deactivation and
preservation of its activity during circulation,
transport to targeted organ or tissue and
intracellular trafficking
A reduction in antigenic activity of the drug
leading to a less pronounced immunological body
response.

21. Specific accumulation in organs, tissues or cells, by
actively targeted polymers or exploiting the known
‘‘enhanced permeability and retention(EPR)
effect’’.
The ability to provide passive or active targeting of
the drug specifically to the site of its action.
In addition to drug and polymer carrier, may
include several other active components that
enhance the specific activity of the main drug.

22. Designing the polymer drug conjugates
In a polymer-drug conjugate, there are
at least three major components.....
1. a soluble polymer backbone
2. a biodegradable linker, and
3. A covalently linked drug which is
deactivated as a conjugate.

23.  Synthetic polymers: PEG (polyethylene glycol), N-(2-
hydroxypropyl)-methacrylamide copolymers (HPMA),
polyethy-leneimine (PEI), polyacroloylmorpholine
(PAcM), polyvinylpyrrolidone (PVP), polyamidoamines,
divinylethermaleic anhydride/acid co-polymer
(DIVEMA), poly(styrene-co-maleic acid/anhydride)
(SMA), polyvinyl alcohol (PVA);
 Natural polymers: dextran, pullulan, mannan, dextrin,
chitosans, hyaluronic acid;
 Biotic polymers: folate, biotin, antibody, poly-A, poly-G
 Pseudosynthetic polymers: PGA, poly(L-lysine),
poly(malic acid), poly(aspartamides), poly((N-
hydroxyethyl)-L-glutamine) (PHEG).

27. FR-mediated endocytosis of folate-drug conjugates
Wei and Philip, Medicinal Chemistry; 2010, 53, 6811-6824

28. ADVANTAGES OF TARGETEDDRUGDELIVERY
Toxicity is reduced by
delivering a drug to its
target site, there by
reducing harmful systemic
effects.
Drug can be
administered in a smaller
dose to produce the desire
effect.
Control of drug
delivery on to a
particular site

29. Enhancement of the absorption of target
molecules such as peptides and particulates.
Avoidance of hepatic first pass metabolism.

30. Rapid clearance of targeted systems.
Insufficient localization of targeted systems
into tumor cells.
Immune reactions against intravenous
administered carrier systems.
Requires highly sophisticated technology
for the formulation.
Requires skill for manufacturing storage,
administration.

31. FUTURE PERSPECTIVE
Nanoparticles provide massive
advantages regarding drug targeting,
delivery with additional potential to
combine diagnosis and therapy Anti-tumour therapy, gene
therapy, radio therapy
This site-specific delivery rotate
towards the gene delivery to
nucleus.
The innovation in this field of research on the
targeted drug delivery in the coming years
would be a shift from “receptor to nucleus”.
Involved in delivery of
virostatics,vaccines and as
vesicles to pass blood brain
barrier

32. REFERENCES
 Vyas s. p.,Khar r. k., 2010, ‘Molecular Basis Of Targeted Drug Delivery’
Targeted & Controlled Drug Delivery System, 6th Edition, CBS
Publishers & Distributors,New Delhi,Page no:38-80, 249-277, 331-387
 Hillery m.,Lloyd w.,2005, ‘Advanced Drug Delivery and Targeting: An
Introduction’Drug Delivery & Targeting, 3rd Edition, Taylor & Francis
Inc,29 West 35th Street, New York,Page no:56-71
 Banker s. g.,Rhodes t. c.,2002, ‘Target Oriented Drug Delivery
System’Modern Pharmaceutics,4th Edition,United States Of
America,Page no:531-580
 Encyclopedia of controlled drug delivery system edited by Edith
Mathiowitz, Pg. no:551-564.
 www.pharmainfo.net/reviews/nanoparticles-and-its-applications-field-
pharmacy
 Nanoparticles –A Review by VJ Mohanraj & Chen Y, Tropical Journal
of Pharmaceutical Research 2006; 5(1): 561-573
 Jain N. K., Controlled and novel Drug Delivery, 1st edition 2001, CBS
Publication; 292 - 301.
 Joshi, H.C., Salil, A., Bughani, U. & Naik, P.K. Noscapinoids: a new
class of anticancer drugs demand bio-technological intervention,
Medicinal Plant Biotechnology, Ed Arora R CAB e-Books CABI (H
ISBN 9781845936785) .2010.

33. Thank
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