it helps for post graduate and graduate students of ayurveda and pharmacy

1. Nanotechnology and its relevance
to Aushadha - Nirman
K V GOPINATH M Pharm PhD,CPhT
Tirumala Tirupati Devasthanams
TIRUPATI
e-mail:gopinath.karnam@gmail.com

2. NANOTECHNOLOGY - DEFİNİTİON
 Nanotechnology is the term derived from the Greek word “nano”
meaning “dwarf”
 Applies the principles in various sciences at a atomic , molecular or
submicron level
 Dimension range: 0.1 – 100 nm (10-1000 nm for pharmaceutical
nanoparticles)
 Definition: “Research and technology development at the atomic,
molecular or macromolecular levels, in the length scale of
approximately 1-100 nanometer range, to provide a fundamental
understanding of phenomena and materials at the nano scale, and to
create and use structures, devices and systems that have novel
properties and functions because of their small and/or intermediate
size”.

3. Advantages of Nanotechnology
 Methods of preparation simple and easy to scale up
 Nano scale components have very high surface areas
 Stable and easily freeze-dried
 Successful tissue targeting of many drugs (antibiotics, cytostatics,
peptides and proteins, nucleic acids etc.)
 Protection of drugs against chemical and enzymatic degradation
 Reduction of side effects of some active drugs

4. Advantages of Nanotechnology
 Mucosal delivery of high molecular weight substances, such as
peptides, proteins, oligonucleotides and plasmids
 Increased solubility and dissolution rate of poorly soluble substances
due to nanosizing improvement of drug bioavailability
 New functions arising from nanosizing, such as improved solubility,
targetability, and adhesion to tissues
 Bionanomaterials:1) Biological materials utilized in nanotechnology
- Proteins, enzymes, DNA, RNA, peptides
2) Synthetic nano materials in biomedical applications
- Polymers, porous silicon, carbon nanotubes

5. Nanoscale Processes and Fabrication
Top-down Approaches Bottom-up Approaches
Optical and x-ray lithography Layer-by-layer self assembly
E-beam and ion-beam lithography Molecular self assembly
Scanning probe lithography Direct assembly
Atomic force microscopic
lithography
Coating and growth
Material removal and deposition
(Chemical, mechanical, or
ultrasonic)
Colloidal aggregation
Printing and imprinting

6. Equipments for Nanoparticles
 Homogenizer
 Ultra Sonicator
 Mills
 Spray Milling
 Supercritical Fluid Technology
 Electro spray
 Ultracentrifugation
 Nano filtration

7. Schematic representation of
Nanosphere Formation –Method 1
Ethyl acetate
+
PLGA
Stirring 1000 rpm
2 hours
Passed through
0.2 µm filter
Aqueous
PVA-Chitosan
2 hours
Passed through
0.2 µm filter
Stirring 1000 rpm
Mixing
3 hours
Stirring 1000 rpm
Homogenize
10 min 13,500 rpm
Water
Stirring 2 hours
Water bath, 40 oC
Add organic to aqueous NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
Ethyl acetate
+
PLGA
Stirring 1000 rpm
2 hours
Passed through
0.2 µm filter
Aqueous
PVA-Chitosan
2 hours
Passed through
0.2 µm filter
Stirring 1000 rpm
Mixing
3 hours
Stirring 1000 rpm
Homogenize
10 min 13,500 rpm
Water
Stirring 2 hours
Water bath, 40 oC
Add organic to aqueous NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2
NH2

8. Polymerization method

9. Different Methods to Prepare Nanospheres
and Nanocapsules
Polymer
Method based on physico-chemical properties of polymer solutions
Phase gelation
Non solvent Salting-out calcium tripolyphosphates
(polymer soluble (polymer soluble in water)
in organic solvent)
Nanocapsules Nanospheres Alginate nanospheres Chitosan nanospheres
Nanospheres

10. microencapsulation techniques-Nanospheres
& Nanocapsules
Polymer
Emulsification
Simple emulsion (W/O) Simple emulsion (O/W) Double emulsion (W/O/W)
(Water soluble) (polymer soluble in organic solvent) (polymer soluble in organic solvent)
Gelation Polymer
precipitation
Solvent evaporation Polymer precipitation İnverse salting out
Solvent extraction Solvent evaporation

11. Nanotechnology Applications
Medicine
- Cancer treatment
- Bone treatment
- Drug delivery
- Appetite control
- Drug development
- Medical tools
- Diagnostic tests
- Imaging
Consumer Goods
Foods and beverages
−Advanced packaging materials,
sensors, and labon-chips for food
quality testing
Appliances and textiles
−Stain proof, water proof and
wrinkle free textiles
Household and cosmetics
− Self-cleaning and scratch free
products, paints, and better cosmetics

12. Nanotechnology Applications
 Medical Nanotechnology or Nano medicine
 Nano medicine is the application of nanotechnology in
medicine, including to cure diseases and repair damaged
tissues such as bone, muscle, and nerve and its monitoring
 Key Goals for Nano medicine:
−To develop cure for traditionally incurable diseases (e.g.
cancer) through the utilization of nanotechnology
−To provide more effective cure with fewer side effects by
means of targeted drug delivery systems

13. Nanotechnology in Health Care -
Detection and Diagnosis
 Nanotechnology offers tools
and techniques for more effective
detection, diagnosis and treatment
of diseases
 Fig: The micro fluidic channel
with nano wire sensor can detect
the presence of altered genes
associated with cancer – J. Heath, Cali.
Insti. of Technology
 Lab on chips help detection and
diagnosis of diseases more efficiently
 Nano wire and cantilever lab on chips
help in early detection of cancer
biomarkers. (Carcinoembryonic antigen –
CEA; Alfa-fetoprotein-CEA; Prostate Specific
antigen –PSA)
 Fig: The nano scale cantilever detects
the presence and concentration of
various molecular expressions of a
cancer cell – A. Majumdar, Univ. of Cal. at Berkeley

14. Nanotechnology in Health Care - Thermal
ablation of cancer cells
 Thermal ablation of cancer cells
− Nano shells have metallic outer layer and silica core kills the
cancer cells by Thermal ablation
− Selectively attracted to cancer shells either through a
phenomena called enhanced permeation retention or due
to some molecules coated on the shells

15. Nanotechnology in Health Care - Treatment
 Targeted drug deliver
− Nano particles containing drugs are coated with targeting
agents (e.g. conjugated antibodies)
− The nano particles circulate through the blood vessels and
reach the target cells
− Drugs are released directly into the targeted cells

16. Nanotechnology Based Drug Delivery
 In biopharmaceuticals, in addition to the main technologies covered
liposomal, monoclonal antibody-based, and polymer-based
technologies host of newer technologies such as nano particles
including various nano dimensional entities such as molecular
imprinted polymers, pro drug delivery, oral, injectable and
implantable, pulmonary, and transdermal and transmucosal delivery
have come up.
 Importance of Drug Delivery Technology to Pharma Industry
􀂉 Drug delivery formulations involve low cost research
compared that for discovery of new molecule,

17. Nanotechnology Based Drug Delivery
� Minimizing the drug use would significantly reduce the effective
cost of drug which would give financial relief to the patients,
� Delivery systems increase commercial opportunity by distinguishing
a drug from competitive threats posed by “me too” drugs and
� Novel means of delivery particularly using nano-carriers, can allow
branded drugs to be rescued from abyss of generic competition (may
be called “resurrection of drug”).

18. SOME SIGNIFICANT NANODEVICES
 Development of one dose a day ciprofloxacin using nanotechnology
 Tumor targeted taxol delivery using nano particles in Phase 2 clinical
trial stage
 Improved ophthalmic delivery formulation using smart hydrogel nano
particles
 Oral insulin formulation using nanoparticles carriers.
 Liposomal based Amphotericin B formulation
� Nano particles for Drug Delivery
- Metal-based nano particles ; - Lipid-based nano particles
- Polymer-based nano particles ; - Biological nano particles

19. Nanotechnology Applications
1) SiO2-Nanoparticles as a new platform for non-viral gene delivery
(favourable size 10 - 50 nm; controlled production possible; excellent phys.-
chemical stability ; many possibilities for chemical modification); Probably
cheaper and safer, but presently not safer.
2) Using Nanotechnology for New Medicines: E.g. Gene-Therapy
mRNA
Modified
genevector
Therapeutic Protein

20. Nanotechnology Applications
3) Brain Drug Targeting : Polysorbate-coated NPs to enhance
penetration to the blood-brain barrier (BBB)
– Mechanism:
– Binding of the NPs to the inner endothelial lining of the brain
capillaries (subsequently, particles deliver drugs to the brain by
providing a large concentration gradient, thus enhancing the passive
diffusion)
– Brain endothelial uptake by phagocytosis
_ A general surfactant effect characterized by a solubilization of the
endothelial cell membrane lipids that would lead to membrane fluidization
and an enhanced drug permeability through the BBB.
_ The NPs could lead to an opening of the tight junctions between the
endothelial cells. The drug could then permeate through the tight junctions
in free form or together with the NPs in bound form

21. Nanotechnology Applications
_The NPs may be endocytosed by the endothelial cells followed by the release of
the drugs within these cells and delivery to the brain.
_The NPs with bound drugs could be transcytosed through the endothelial cell layer
_The polysorbate 80 used as the coating agent could inhibit the efflux system,
especially P- glycoprotein (P-gp)
4) Semiconductor Nano Crystals or “QUANTUM Dots TM
” or
Biodegradable bio polymers for ex-vivo optical diagnostics and
some form of hybrid biodegradable nano capsule with MRI
contrast agent core for in-vivo simultaneous diagnostics and
therapeutics (“theragnostics”).

22. Nanotechnology Applications
 Nanoelectromechanical System
(NEMS) Sensors
− NEMS technology enables
creation of ultra small and highly
sensitive sensors for various
applications
− The NEMS force sensor shown in
the figure is applicable in pathogenic
bacteria detection
Fig : A NEMS bacteria sensor

23. Nanotechnology Applications
5) Nano medicine - Continuous Therapy for
Preventing Cancer in Astronauts:
Engineered multilayered nano particles targeted to
radiation-damaged cells can initiate repair of damaged
DNA using DNA repair genes manufactured inside
individual living cells under the control of molecular
biosensor switches.
6) Nanoparticles in cancer therapy : Increase in
antitumor efficacy; Reduction of systemic side-effects;
Selective delivery of oligonucleotides to tumor cells ;
Reversion of multidrug resistance in tumor cells;
7) Targeted delivery of antibiotics using
nanoparticles: Challenge is to design the means of
carrying an antibiotic in a form that is able to be
endocytosed by phagocytic cells and then released into
these cells. Nanoparticles are one of the main carriers
developed for these logistic strategies

24. Nanotechnology Applications
Targeting of intracellular
bacteria with antibiotic
colloidal carriers:
liposomes or nanoparticles.

25. Nanotechnology Applications- DNA
Sequencing
8) In DNA Sequencing: DNA molecules, under
the influence of an electric field, are forced
through nano-scale channels (~100 nm) on a
“gel biochip”. The molecules deform and
stretch to pass through the small channels.
 This process separates DNA fragments by
length.
 This is part of the method used to sequence the
DNA in the human genome and in
identifying a unique DNA “fingerprint”.

26. Nanotechnology Applications - Immunoisolation for
Cell-encapsulation therapy
9) Liver Dysfunction: Encapsulation of Hepatic Cell
Pancreas Dysfunction: Encapsulation of Islets of Langerhans
Disorders of the CNS: Parkinson’s, Alzheimer’s
Pre-requisites for cell encapsulation
– continued and optimal tissue/cell supply
– maintenance of cell viability & function
– successful prevention of immune rejection
Nonporous Silicone-based biocapsules serves as Artificial
Pancreas(Desai et al.)

27. Nanotechnology Applications
10) Targeting Tumours: « Smart Bombs »
 Conventional Therapy: Chemotherapy that poisons surrounding
tissue
 Strategy: Block angiogenesis selectively at tumor site
 Nanoparticle: DNA + Cationic Polymer directed at tumourous cells
 Starves blood cells

28. Nano engineering – Bio -
analogous Structures
 Bone-cartilage composite ?
 Muscle ?
 Brain-machine Interface ?

29. CHALLENGES & Methods of
Drug Delivery
 Prevention of drug from biological degradation (Oral dosage form)
 Effective Targeting ( Inhalation)
 Patient Compliance (Tran dermal)
 Cost effectiveness (Implantation)
 Product life extension (Injections)