Nanotechnology in

Drug Delivery System

MT5009 ANALYZING HI-TECHNOLOGY OPPORTUNITIES

FOONG SHI WEN A0133491

LAM CHEE YEN, KELVIN A0132425

SEOW WHEI-ZHNG A0132427

• 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

• 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

Nanotechnology

Science, engineering, and technology conducted at the nanoscale

(1-100nm), where unique phenomena enable novel applications

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?

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

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

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?

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

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

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

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

• 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

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

Increasing Global Investments in

Nanotechnology

Expectation of lucrative

market

U.S. sets aside

the highest amt

of funding for

Nanotechnology

Increasing Global Investments in Nanotechnology

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

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

Main Areas of

Nano Drug Application

Cancer, Infection Control, Cardiovascular disease

The big picture on nanomedicine: the state of investigational and approved nanomedicine products

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

Evolution of Controlled DDS

Facing the Truth about Nanotechnology in Drug Delivery. ACS Nano. 2013 September 24.

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

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

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

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 PEGylatedLiposomes (80-90nm)

AIDS-relatedKaposi’s sarcoma,Breast cancer

IV Passive targeting,accumulate at tumorsites due to small size

Much lesser cardiotoxicity

2006 Peg-l-asparaginase

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)

Variouscancers

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 Tumorprogression(23 wks vs 16.9 wks)

Examples of Nano DDS currently in the market

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 DesignationApproved 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 IIIFast Track Designation

IV Heat-activated (≥39.5∘C) release of drugs withinseconds

Doxorubicin, Cyclophosphamide

Non-PEGylatedLiposomes

MetastasticBreast cancer

Phase III in USApproved 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

• 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

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, forthcoming2) Jeffrey L. Funk, What Drives Exponential Improvements, California Management Review, August 2013

Creating New Material that exploit phenomenon

Source: https://news.mit.edu/2014/glowing-magnetic-nanoparticles-1009https://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

• 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

• 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)

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

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)

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

Improvements and Advances of DDS

Summary

• New nanoparticles with new coating

• Smart capsule, iPill, NanoBotsNew 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 pillsGovernment Policies

and Regulations

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.

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/2015/02/09/materials-science-assistant-professor-uses-affordable-tools-to-create-nanoparticle-catalysts-and-drug-delivery-systems/

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.

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)

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)

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

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)

Thank You