1. NANOTECHNOLOGY IN DRUG DELIVERY
DR. POOJA ROY
DEPARTMENT OF PHARMACOLOGY,
VIMS & RC, BANGALORE

2. OUTLINE
 need for new delivery systems
 Definition – nanotechnology
 Definition - nanomedicine
 Nanomedicines
o Nanopores
o Quantum dots
o Fullerenes
o Nanoshells
o Dendrimers
o Nanorobots

3. Need for New Drug Delivery
Systems
 Introducing a new drug to market costs on an
average US $ 897 million / 4485 crores
 Process for approval may take upto 15 yrs
 Already existing time tested drugs are effectively
used by interdisciplinary approaches to increase
their efficacy

4. Its Advantages..
 To improve the drug delivery i.e. increases drug
bioavailability in required zone
 Prevent / minimize harmful side effects
 Minimize drug degradation and loss
 Prolonged duration of drug action
 For better patient compliance

5. Routes of Administration
 ORAL
 SUBLINGUAL
 RECTAL
 INHALATION
 PARENTERAL .

6. NEWER DELIVERY SYSTEMS
 Ocusert , Progestasert
 Liposomes , Polymer based drug delivery system
 Insulin pen , Insulin pump
 Transdermal drug delivery system , Prodrugs
 Nanomedicines (Nanotechnology)
 Iontophoresis , phonophoresis
 Computerized miniature pumps , Monoclonal
antibodies

7. NANOTECHNOLOGY &
NANOMEDICINE
Breakthroughs in Healthcare
Enabled by Nanotechnology

8. BIGGER ISN’T ALWAYS BETTER
- SIR RICHARD FEYNMAN (1959)

9. HISTORY
 Richard Feynman – 1959
lecture at California
Institute ofTechnology
 Title :
There is plenty of room
at the bottom
(the idea of building
objects from the bottom
up, i.e. from individual
atoms )

10. HISTORY
 Mid 1980s:
Eric Drexler (1986)-
published Engines of
Creation.
 Envisioned a molecular
nanotechnology
discipline – allow to
fabricate products from
the bottom up and
allows every molecule to
be inserted into its
specific place

11. NATIONAL NANOTECHNOLOGY
INITIATIVE - DEFINITION
R & D at atomic, molecular and
macromolecular levels in sub-100 nm range
(1 to 100 nm).

12. COMPARISON OF SIZES
(WITH LIVING SYSTEM)

14. NANOMEDICINE
Monitoring, repair, construction, and control of
human biological systems at the molecular level,
using engineered nanodevices and
nanostructures

15. NANOTECHNOLOGY AND NANOMEDICINE
NANOTECHNOLOGY NANOMEDICINE
 Science dealing with
nanoparticles.
 E.g.- nanodevices like Q-
dots, dendrimers
widespread and broadly
marketed.
 Established discipline
 Clinical application of this
science to the practice of
medicine.
 Yet to find their way into
clinical devices.
 Nascent stage of
development

16. Characteristics of
Nanoparticles
 Target specificity
 Extreme small size
 Encapsulation efficiency
 Carry high concentrated drug
 Zeta potential (surface charge)
 Efficient drug release

17. NANOPORES
 Tiny cell containing chambers within single
crystalline silicon wafers
 Chambers interface with surrounding biological
environment
 Present high density of pores

18. NANOPORES
 Pores large enough to allow passage of small
molecules like – insulin, glucose and oxygen
 Pores not large enough to permit immune
system molecules – Ig’s, graft borne virus particle
 Thus immunosuppressants not required

19. EXAMPLES OF NANOPORES
 Immunoisolated encapsulated rat pancreatic
cells
 Microcapsules containing isolated islets of
Langerhans cells, can be implanted beneath skin
of diabetic patients
 Similarly can be used to replenish any enzyme or
hormone deficiency conditions

20. NANOPORES IN FUTURE
 In neurodegenerative disorders like Alzheimer’s
disease and Parkinsonism.
 Encapsulated neurons placed in brain

21. ThingsUsedsofar..
Fluorescent tags
 Used in HIV test, in experiments to image the
inner functions of cells
 Limitations –
1) Different dyes for different colour
2) Colour matched lasers for each dye to fluoresce
3) Dye colours fade quickly after one use

22. The New Era..
QUANTUM DOTS
 Colour defined by particle size and composition.
 Linked to biomolecules to form long lived
sensitive probes to –
a) Identify specific compounds
b) To track biological events

23. Structure and application of
Quantum (Q dots) dots

24. FULLERENES
 Form of C-60 composed of C-atoms arranged in a soccer
ball like configuration
 Also called bucky balls
 Ideal drug delivery vehicles due to their size and shape
 Good bioavailability , low toxicity even at high dosages

25. Is it fullerenes or soccer
balls?

26. USES OF FULLERENES
 As anti-viral agents (e.g.- HIV)
 Anti-tumor and anti-cancer therapy.
 Anti-oxidants
 Anti-apoptotic agents (e.g.- Parkinson’s disease)

27. NANOSHELLS
 Developed at Rice University in Houston
 Platform for nanoscale drug delivery
 Di-electric metal nanospheres with a core of
silica and a golden coating
 Each slightly larger than polio virus

28. GOLD NANOSHELLS

29. Gold Nanoparticle

30. NANOSHELLS IN CIRCULATION

31. MECHANISMOFACTIONOFNANOSHELLS
 Consist of drug containing tumour-targeted
hydrogel polymer injected into the body
 Shells accumulate near the tumour
 Heated by IR laser, polymer melts and releases
drug at the desired site

32. Nanoshell Delivery causes Cancer Cell Death

33. NanospectraBiosciences
 At University ofTexas, developing commercial
applications of nanoshells
 Animal studies carried out to specifically target
micro-metastasis

34. CANCER SMARTBOMBS
 FDA approved targeted
radioimmunotherapeutic agents
 Deliver radioactiveYttrium or Iodine to
lymphoma directed antibody (anti CD-20
antibody).

35. NANOGENERATOR
 Alpha emitting actinium based ,use
internalizing monoclonal antibodies to
penetrate the cell.
 Useful in – leukaemia
lymphoma
breast CA
Ovarian CA
Neuroblastoma

36. DENDRIMERBASEDDEVICES
 Tree like synthetic nanostructured particle with
branches emanating out.
 Branches act as hooks to which important
molecules like DNA can be attached.
 Enters cells by endocytosis.

37. DENDRIMERS

38. TECTO- DENDRIMERS
 Single core dendrimer surrounded by additional
dendrimer modules of different types
 Ethylene diamine core surrounded by folic acid,
fluorescein, and methotrexate
 100 fold improvement in cytotoxic response to
methotrexate

39. GENOMIC REVOLUTION
 At least one unique protein has been identified in
half dozen cancers
 As genomic revolution progresses, mostly
proteins unique to each type of cancer will be
identified
 Dendrimers will target these proteins

40. GENOMIC REVOLUTION

41. LIPID BASEDDRUGS
 First nanodrugs to be used
 Phospholipids chemically
 ABRAXANE – used for metastatic breast cancer
 A formulation of anti-cancer drug Paclitaxel with
micro-fine albumin
Advantages
 Capable of paclitaxel delivery to the body at a 50%
higher dose over 30 mins
 Avoids toxic effects.

42. CONTD….
 Paclitaxel , due to its poor
solubility in blood,if given
bound with various solvents
can cause hypersensitivity
reactions
 This may neccesitate of
steroids administration which
may in turn cause
Hyperglycemia
Immunosuppression
Insomnia

43. Multicomponent Targeting Strategies

44. NANOROBOTS
 Has carbon nanotube
body, biomolecular
motor that propels it
and peptide limbs to
orient itself
 in vivo use

45. NANOROBOTS
Used for –
 Targeted drug delivery
 Taking biopsies
 Reopening of blocked arteries
 Magnetically controlled karyobots and
cytobots to perform wireless intracellular
surgery

46. CARDIOVASCULAR NANOMEDICINE
 FDA approved
nano-cardio products
not available
 May help in preventing
blood vessel occlusion
by thrombi (detects
even small thrombi)

47. NEUROLOGICAL NANOMEDICINE
 Repair of CNS following trauma
 Critical target
To be able to take brain biopsy to detect beta
amyloid plaques (currently possible only after
death at autopsy) in Alzheimer’s disease

48. ONCOLOGYANDNANOMEDICINE
 Advantages over conventional cancer
therapy ---
higher payload capacity
increased blood circulation times
improved anti-tumor efficacy
reduced toxicity to healthy tissues

49. ONGOING CLINICAL TRIALS
 Nanoparticles in ophthalmology
(Retina implants, age-related macular
degeneration, glaucoma)
 Nanoparticles in OA and inflammatory arthritis

50. NANOMEDICINEANDFUTURE
 More medical benefits in next 10 yrs
 Exhaustive research both in India and abroad
 Government granting huge funds

51. REFERENCES
 C A Haberzettl. Nanomedicine: destination or
journey?.INSTITUTE OF PHYSICS PUBLISHING
NANOTECHNOLOGYNanotechnology 13 (2002) R9–
R13.
 K. John Morrow, Jr, RajBawa, ChimingWei. Recent
Advances in Basic and Clinical Nanomedicine. Med
Clin N Am 91 (2007) 805–843.
 Robert A. Freitas, Jr. Current Status of
Nanomedicine and Medical Nanorobotics. Journal
of Computational andTheoretical NanoscienceVol.2,
1–25, 2005.

52. REFERENCES
 ELVIN BLANCO, CHASEW. KESSINGER, BARAN D.
SUMER, JINMING GAO. Multifunctional Micellar
Nanomedicine for CancerTherapy. 2009 by the Society for
Experimental Biology and Medicine.
 S. MoeinMoghimi,A. Christy Hunter, and J. Clifford Murray.
Nanomedicine: current status and future prospects. The
FASEBJournal. 0892-6638/05/0019-0311.
 Volker Wagner, AnwynDullaart,Anne-Katrin Bock & Axel
Zweck. The emerging nanomedicine landscape. NATURE
BIOTECHNOLOGYVOLUME 24 NUMBER 10 OCTOBER
2006.

53. THANK YOU