These slides use concepts from my (Jeff Funk) course entitled analyzing hi-tech opportunities to show how nanotechnology for drug deliver is becoming economically feasible.

1. Nanotechnology in
Drug Delivery System
MT5009 ANALYZING HI-TECHNOLOGY OPPORTUNITIES
FOONG SHI WEN A0133491
LAM CHEE YEN, KELVIN A0132425
SEOW WHEI-ZHNG A0132427

2. • Introduction to Nanotechnology in Drug Delivery
• Definition of Nanotechnology, Nanomedicine, Nano DDS
• Nano DDS – Vehicle, Cargo, Route, Targeting
• Nano vs Traditional Drug Delivery
• Current Status of Market & Advances
• Changing Economics of Nano Drug Delivery
• Market growth that shows optimism
• Drug delivery system that is currently in market
• Drug that are going to be released in near future (clinical trial)
• Economical Feasibility of Nanotechnology DDS
• Improvement and advances over the next 5 to 10 years
• Current Challenges / Issues
• Drivers for Market Adoption
• Entrepreneur Opportunities
• Conclusion
Agenda

3. • Introduction to Nanotechnology in Drug Delivery
• Definition of Nanotechnology, Nanomedicine, Nano DDS
• Nano DDS – Vehicle, Cargo, Route, Targeting
• Nano vs Traditional Drug Delivery
• Current Status of Market & Advances
• Changing Economics of Nano Drug Delivery
• Market growth that shows optimism
• Drug delivery system that is currently in market
• Drug that are going to be released in near future (clinical trial)
• Economical Feasibility of Nanotechnology DDS
• Improvement and advances over the next 5 to 10 years
• Current Challenges / Issues
• Drivers for Market Adoption
• Entrepreneur Opportunities
• Conclusion
Agenda

4. Nanotechnology
Science, engineering, and technology conducted at the nanoscale
(1-100nm), where unique phenomena enable novel applications

5. Nanomedicine
http://www.britishsocietynanomedicine.org/what-is-nanomedicine.html
• The medical application of Nanotechnology
• Diagnosis, prevention and treatment of diseases
• Usage of nanoparticles to improve the behavior of drugs
Different structures of
nanoparticles & their
approx. sizes
They are in similar size
range as biological
nanostructures
Q: How do the
Nanoparticles
carry drugs?

6. Ans.: Nanoparticles
act as a vehicle on
which the drugs are
encapsulated within
or chemically bonded
• Usage of engineered nanoparticles to deliver drugs in a more
targeted, efficient way, with less unpleasant side effects to patients
Liposome: Most
commonly used
nanoparticle
Nano Drug Delivery System
Let’s look at Liposome
as an example

7. Nano Drug Delivery System –
Vehicle & Cargo
Liposome as a
Nano drug vehicle
Specifically targets
certain molecules
to bind to
Nano drugs within
are protected
during travel
Biocompatible as it has similar membrane as human cells
http://sitn.hms.harvard.edu/flash/2011/materials-for-drug-delivery/
Nano drugs of
different solubility
properties are
carried within the
Liposome

8. Injections
Etheridge M.L., Campbell S.A., Erdman A.G., Haynes C.L., Wolf S.M., McCullough J., The big picture of nanomedicine: the state of investigational
and approved nanomedicine products, Nanomedicine: NBM 2013;9:1-14
Most commonly used route, as
the drug can be administered
directly to site and thus effect
is more rapid
Nano Drug Delivery System - Route
Q: How are Nanoparticles carrying drug administered into body?

9. Nano Drug Delivery System - Targeting
Q: How do the Nanoparticles deliver drugs to targeted
tissues?
• Purely Size & Geometry dependent
mode
• Normal blood vessels:
• Cell walls have tight junctions
with spaces smaller than the
Nanoparticle
• Nanoparticle carrying drug is
not able to enter, preventing
toxicity to normal tissues
• Cancerous blood vessels:
• Cell walls are dilated with large
gaps (200-1200nm) &
compromised lymphatic
drainage
• Highly permeable for
nanoparticles up to dia.400nm
to enter and preferentially
accumulate at tumor sites
Passive
Targeting

10. Nano Drug Delivery System - Targeting
• Not dependent on size or geometry
• Affinity ligands (e.g. antibodies,
DNA/RNA) are attached to
Nanoparticle surface
• This allow the Nanoparticle carrying
drug to recognize and bind to target
cells having specific receptors on
their surfaces, e.g. tumor cells
• After the nanoparticle is bound to
the target cells, the drugs carried
within is released inside the target
cells
Active
Targeting
http://www.medscape.com/viewarticle/770397_3

11. http://nano.cancer.gov/learn/
http://www.nature.com/labinvest/journal/v82/n5/full/3780460a.html
Nano vs. Traditional Drug Delivery
Criteria Traditional Nano
Specificity Drugs will pass through
unaffected sites before
reaching affected site
Delivered in more
targeted manner to the
affected site
Dosage
Release
Higher initial dosage
required
No control ability
Able to control dosage
by trigger, requirement,
and even time-release
Efficacy Drug concentration in
affected site is low
Drug concentration in
affected site is more
optimized
Side Effects Inevitable exposure of
unaffected sites to drugs
Lesser exposure of
unaffected sites to drugs

12. http://nano.cancer.gov/learn/
http://www.nature.com/labinvest/journal/v82/n5/full/3780460a.html
Nano vs. Traditional Drug Delivery
Nano
Drug
Delivery
Controlled
Release
TargetingEffective

13. • Introduction to Nanotechnology in Drug Delivery
• Definition of Nanotechnology, Nanomedicine, Nano DDS
• Nano DDS – Vehicle, Cargo, Route, Targeting
• Nano vs Traditional Drug Delivery
• Current Status of Market & Advances
• Changing Economics of Nano Drug Delivery
• Market growth that shows optimism
• Drug delivery system that is currently in market
• Drug that are going to be released in near future (clinical trial)
• Economical Feasibility of Nanotechnology DDS
• Improvement and advances over the next 5 to 10 years
• Current Challenges / Issues
• Drivers for Market Adoption
• Entrepreneur Opportunities
• Conclusion
Agenda

14. Nanotechnology in
Drug Delivery Market
GBI Research,2010
Opportunities
for New Drug
Delivery
Companies
Nanotoxicity of
Nanomaterials
Market Growth
Need of
Understanding
Biological
behaviour
Need of
Understanding
Distribution
Pattern of
Nanomaterial
Licensing
Opportunities
Opportunities Unmet Needs

15. Increasing Global Investments in
Nanotechnology
Expectation
of lucrative
market

16. U.S. sets aside
the highest amt
of funding for
Nanotechnology
Increasing Global Investments in
Nanotechnology

17. U.S. Investments in Nanotechnology
16.5% + 25.7%
42.2% of NNI Budget is
allocated for
Commercialization &
technology transfer!
National Nanotechnology
Initiative (NNI) –
U.S Govt R&D initiative
involving 20 department,
independent academic
and industry agencies
U.S Federal Budget 2016
sets aside $1.5 billion for
NNI. Cumulatively, $22
billion since NNI inception in
2001
THE NATIONAL NANOTECHNOLOGY INITIATIVE, Mar 2015

18. U.S. Focus on
Nano-based Biomedical Research
DHHS/NIH
(nanotechnology-
based biomedical
research at the
intersection of life
and physical
sciences) is
allocated $448.6 mil
or 30% of total NNI
budget in 2016
signifies emphasis
on accelerating
improvement in
biomedical, e.g.
nanomedicine

19. Main Areas of
Nano Drug Application
Cancer, Infection Control,
Cardiovascular disease
The big picture on nanomedicine: the state of investigational and approved nanomedicine products

20. Contribution of Nano-Enabled
Products on Cancer
The big picture on nanomedicine: the state of investigational and approved nanomedicine products
• At present, cancer is one of the largest therapeutic areas in
which nano-enabled products have made major
contributions
• Cancer is a prime focus for nanopharmaceutical R&D

21. Evolution of Controlled DDS
Facing the Truth about Nanotechnology in Drug Delivery. ACS Nano. 2013 September 24.

22. Components of DDS
Nano Drug Delivery System
Structure-Based
• Microneedle
arrays
through skin
painlessly
• Microneedle
patch for
vaccine
delivery
Electrically-Based Vehicle-Based
• Electrically
controlled drug
delivery
nanocomposite
composed of
graphene oxide
(GO) deposited
inside a
conducting
polymer
• Nanosponges
are a promising
vehicle in
treating cancer
• Releasing
medication at
the tumor site
at a steady,
controlled rate
Targeting Strategies
• Plant virus
nanoparticles
that can
target
prostate
cancer cells
July 2013 Newsletter, NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERING

23. Structure-Based - Microneedle
Silicon microneedles have been fabricated to
serve as neural probes by dicing a silicon
substrate to create a grid pattern of deep
grooves and then acid etching the resulting pillars
to create sharpened probe tips
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419303/
Price of Silicon microneedles
is expected to decrease

24. Electrically-Based - Nanocomposite
The high level of temporal control and dosage flexibility provided by the
electrically controlled graphene oxide nanocomposite drug delivery
platform makes it suitable for on-demand drug delivery
http://pubs.acs.org/doi/abs/10.1021/nn406223e
Price of nanocomposite is
expected to decrease

25. Vehicle Based & Targeting Strategies
Journal of Nanomaterials, Volume 2013, Article ID 629681, 12 pages
http://dx.doi.org/10.1155/2013/629681
Year Drug
(Cargo)
Nanoparticle
(Vehicle)
For Route Features of Vehicle Improvement over
non-nano version
1995 Doxorubicin PEGylated
Liposomes
(80-90nm)
AIDS-
related
Kaposi’s
sarcoma,
Breast
cancer
IV Passive targeting,
accumulate at tumor
sites due to small size
Much lesser
cardiotoxicity
2006 Peg-l-
asparaginas
e
Polymer–
protein
conjugate
Leukemia IM, IV Active targeting and
catalysing
asparagine to
aspartic acid &
ammonia, depriving
Leukemic cells of
asparagine
Longer drug
retention
(Half life 357h vs
20h)
Less allergic
reaction
(11% vs 25%)
2005 Paclitaxel Albumin
nanoparticles
(100-200nm)
Various
cancers
IV > Non polar vehicle,
ideal for hydrophobic
Paclitaxel
> Active targeting to
protein that is
expressed by cancer
cells
Faster response
rates (33% vs 19%)
Delay Tumor
progression
(23 wks vs 16.9 wks)
Examples of Nano DDS currently in the market

26. Vehicle Based & Targeting Strategies
Drug
(Cargo)
Nanoparticle
(Vehicle)
For Current
Clinical Trial
Route Features of Vehicle
MicroRNA-
122
Liposome with
high-affinity
collagen
Pancreatic,
bile duct,
gastric,
colonic and
stomach
cancers
Phase II/III
Fast Track
Designation
Approved in
Philippines
IV Active Targeting to
cancer collagen
1st of its kind (Gene
therapy of cancer) selling
in market
Doxorubicin Heat-activated
Liposomes
Liver cancer,
Breast cancer
Phase III
Fast Track
Designation
IV Heat-activated (≥39.5∘C)
release of drugs within
seconds
Doxorubicin,
Cyclophosp
hamide
Non-PEGylated
Liposomes
Metastastic
Breast cancer
Phase III in US
Approved in
EU and
Canada
IV Passive targeting
Quick release of cargo
(90% released in 24h)
Examples of upcoming Nano DDS
Journal of Nanomaterials, Volume 2013, Article ID 629681, 12 pages
http://dx.doi.org/10.1155/2013/629681

27. • Introduction to Nanotechnology in Drug Delivery
• Definition of Nanotechnology, Nanomedicine, Nano DDS
• Nano DDS – Vehicle, Cargo, Route, Targeting
• Nano vs Traditional Drug Delivery
• Current Status of Market & Advances
• Changing Economics of Nano Drug Delivery
• Market growth that shows optimism
• Drug delivery system that is currently in market
• Drug that are going to be released in near future (clinical trial)
• Economical Feasibility of Nanotechnology DDS
• Improvement and advances over the next 5 to 10 years
• Current Challenges / Issues
• Drivers for Market Adoption
• Entrepreneur Opportunities
• Conclusion
Agenda

28. Nano DDS -Economic Feasibility
Economic
Feasibility
Improved Processes
- Route of Delivery
- Targeting Strategies
Government
Policies and
Regulations by
FDA
- Reduction of
Transaction costs
Geometric Scaling
- Increase in Scale
- Reduction in Scale
Creating New
Materials
- New Nanoparticles
- New Drugs
Source:
1) Jeffrey L. Funk and Pei-Sin Ng, When do New Technologies Become Economically Feasible? The Case of Three-Dimensional
Television, Technology and Society, forthcoming
2) Jeffrey L. Funk, What Drives Exponential Improvements, California Management Review, August 2013

29. Creating New Material that exploit phenomenon
Source:
https://news.mit.edu/2014/glowing-magnetic-nanoparticles-1009
https://www.youtube.com/watch?v=KdHksgstcXY
New Nanoparticles
- can be tracked within body or inside a cell
- can seek out and bind with particular molecules
glow with color-
coded light
manipulated
with magnets
have a coating
of a bioreactive
substance
Improvements:
• May add additional materials to the particles’
coating
• Either for diagnosis or treatment

30. • A "smart capsule" can be
manipulated when and where the
medicine was released inside a
simulated gastrointestinal tract.
• When the capsule reaches the
organ, a magnet worn on the
patient's hip would trigger electrical
components in the device to release
the medicine.
Creating New Material that exploit phenomenon
Source:
http://www.jconline.com/story/news/college/2015/07/26/purdue-smart-capsule/30699373/
Improvements:
• Release (medicine) into a specific location
more accurately and timely
• Manipulated by Magnet

31. • Philips’ Intelligent Pill (iPill) can be programmed to deliver
medicine in a controlled fashion according to a pre-defined drug
release profile which is to be created per patient and condition. It
is mostly focused on treating conditions in different areas of the
intestine based on the acidity of its surroundings (pH Value).
Creating New Material that exploit phenomenon
Source:
http://thefutureofthings.com/3794-philips-smart-pill-to-deliver-drugs/
Improvements:
• FDA approved camera pills for
diagnostic application
• Programmable
• Based on patient’s condition in drug
release profile (customised)

32. New Process for
moving nanoparticles
Nanobots for targeting cancer cells
• Researchers at the Israel Institute of Technology (Technion) have now
found an artful way to propel such 'bots.
• They created a "nanoswimmer" the width of a silk fiber, made of
several links of polymer and magnetic nanowires. The team can
control exactly where the nanobots finish up -- at a particular organ,
say -- by modulating the field.
Source:
http://www.engadget.com/2015/06/19/swimming-nanobots-target-cancer/
https://www.youtube.com/watch?v=eRxyN9yxOP0
Improvements:
• Control exactly where the nanobots
• Reduce need for surgery, speedy
recovery, lower risk

33. New Process for
moving nanoparticles
• The proposed Local Electromagnetic
Steering System (LESS) uses a small
electromagnet that is attached to a
robotic manipulator to steer the
nanoparticles inside the blood vessels.
• The main advantage of LESS is that it
significantly reduces the cost (a few
thousand dollars) and also the size of the
system; as compared to multi-million dollar
MRI-based drug delivery in chemotherapy
as one of the important procedures in the
cancer therapy.
Source:
http://contest.techbriefs.com/2015/entries/medical/6254
Improvements:
• Reduction in size (LESS)
• Reduction in costs (a few thousands dollars)

34. New Process for
producing nanoparticles
Materials science assistant professor uses affordable tools to create
nanoparticle catalysts and drug-delivery systems
 His team set out to develop a low-cost approach to nanoparticles
synthesis - low-cost “scissor” to chop blocks of metals into small particles
while also forming and organizing other layers on the metal surface to
create an onion-like nanoassembly.
 The advantage is that when the drug is attached to the squishy particle it
can respond to acidity changes in the body. The drug would only be
released in regions with high pH, a common feature of tumors and
inflammation; thereby, attacking the disease or foreign object only
where needed.
Source:
http://news.engineering.iastate.edu/2015/02/09/materials-science-assistant-professor-
uses-affordable-tools-to-create-nanoparticle-catalysts-and-drug-delivery-systems/
Improvements:
• Affordable tools

35. Improvements and Advances of DDS
Summary
• New nanoparticles with new
coating
• Smart capsule, iPill, NanoBots
New Materials
• Manipulated with magnets
• Programmable (drug release
profile)
New Processes
• Reduction in size of manipulators
(MRI vs LESS)
• Reduction in size in production
tools
Geometric Scaling
• FDA approval in camera pills
Government Policies
and Regulations

36. Challenges and Issues
• According to the Pharmaceutical Research Manufacturers
of America (PhRMA) in 2009, the average total cost to push
a new drug through development in the United States is
more than $800 million.
• The process takes an average of 12 to 15 years, leaving only
five to eight years of U.S. patent protection. PhRMA further
notes that just one in 5,000 new compounds survives the
process to become a new drug in the marketplace.

37. Drivers for Market Adoption
Nano
DDS
Development in
Drug Delivery Devices
Lowering cost
for large-scale
production
Increase in take-up rate
by Health Institutions and
Consumers [Demand]
Improvement in
performance
and accuracy
of Nano DDS
Source:
IntelliCap electronic oral drug
delivery technology wins prestigious
European ‘High-Tech Innovation
Award’
http://news.engineering.iastate.edu/2
015/02/09/materials-science-assistant-
professor-uses-affordable-tools-to-
create-nanoparticle-catalysts-and-
drug-delivery-systems/

38. Types of Entrepreneurial Opportunities
Top left:
“Smart” insulin patch which can
actively controls blood sugar
levels
Top Right:
Red Dot Design Award for
KiCoPen , Smart Insulin Pen
Bottom:
SmartDose system from West
Pharmaceutical Services.

39. Types of Entrepreneurial Opportunities
• Disease Diagnosis and Imaging
• Preventing and Treating Diseases
• Smart Drug Delivery System and Device
• Skin Patches and Micro needles (3M and Novinject)

40. Future Trends
The use of electronics opens up new possibilities in the era of
Smart Drug Delivery System
• Active Feedback System (Health Care Workers and Patients)
• Programmable Drug Release Profile
• Improve Ease of Use (self-administer)

41. Nano Drug Delivery still has lots of room
for improvement
Facing the Truth about Nanotechnology in Drug Delivery. ACS Nano. 2013 September 24; 7(9): 7442–7447. doi:10.1021/nn404501g.
• By using Nanoparticles
to delivery drug, >95%
administered drug still
ends up at non-target
site (non-tumor)
• BUT, it is still 5x more
efficient delivery than
non-nano drug
delivery method
• This 5x more efficient
delivery can be
exploited for
maximizing drug
efficacy
A: Traditional drug solution
B: Nanoparticle formulation
5x more

42. Conclusion
• The use of nanotechnology for diagnosis and treatment of
cancer and other diseases is largely still in the research and
development phase
• We will need to find new materials (e.g. new nanoparticles)
that are appropriate for more specific applications
• We will also need to find new processes (e.g. new
nonmanufacturing process) that produce nanoparticles
cheaply and in large quantities
• Increasing alliance between pharmaceutical companies and
DDS Research Institutions
(Invention  Innovation  Commercialisation)

43. Thank You