Targeted Drug Delivery--Technologies

and Applications

Novel Drug Delivery Systems and Clinical Trial

Management China 2013

Aiswariya Chidambaram
28th November 2013
 Focus Points

Importance of Targeted Drug Delivery

Segmentation of Targeted Drug Delivery

Technology Capability Drug Delivery Carriers

Technology Value Chain

Targeted Drug Delivery Key Innovations

Targeted Drug Delivery Drivers and Challenges

Key Technology Developments Drug Delivery Carriers

Focus Points
Life Cycle Analysis of Drug Delivery Systems

Demand Side Analysis

Potential Applications by Therapeutic Area

Patent Distribution and Publishing Trends

About Frost & Sullivan

2
 Importance of Targeted Drug Delivery

Targeted drug delivery is a system of drug delivery which increases the concentration of the drug in specific organs and tissues
relative to the others. This helps improve the efficacy of the drug while reducing side effects. Cancer, autoimmune diseases,
neurological disorders, pulmonary diseases, cardiovascular diseases and most other conditions that require effective, safe ,
specific targeting of certain receptors or direct delivery into the organ are attractive targets for targeted drug delivery.

Criticality of Targeted Drug Delivery Physiological and Biological Barriers to Drug Delivery

Blood Brain
Mucous Barrier
Maximize Barrier (several
precision (lungs, nose, factors lead to
and cancer ineffective
cells) delivery to
brain)
Ineffective
Subcellular Ligand
Targeting Targeting
(cytosol, ER, (disease
nucleus specific
targeting) ligands on
cell surface)
Other
Size Barriers
Minimize Moderate Exclusion (pH,
toxicity release (size barrier osmotic
of different potential,
membranes) electric
charge)
Source: Frost & Sullivan

3
Segmentation of Targeted Drug Delivery

Oncology and neurology are the two most widely

researched diseases for targeted drug delivery.

Delivery to the lungs, eyes, and nose are other areas of

interest as targeting these organs is relatively difficult.
Lipid-based
Liposomes - nanoliposomes, stimuli responsive
Polymer-based
liposomes, and conjugated liposomes with other functional
attributes are gaining attention from researchers.

Inorganic Nanoparticles Peptides and nucleic acids -Chimeric peptides are formed
Targeted Drug
Delivery when a drug that is normally not transported through the
Carriers BBB is conjugated to a brain drug-targeting vector.
Magnetic Particles

Engineered polymers - PEG, polymeric nanomicelles and

Nucleic Acid/ Peptide-
based other co-polymers; polymers designed to respond to
specific biological changes (such as pH, temperature,
chemicals and so on) so that the drug load is released
Cell-based
only upon stimulation.

Conjugates - antibody conjugated liposomal carriers,

multifunctional nanocarriers, and other particles that form
conjugates with the drug.
Source: Frost & Sullivan

D4C1-TI 4
 Technology CapabilityLipid-Based Carriers

Liposomes are widely used for insoluble drugs and advances in conjugation technologies is enabling them to be used as
targeted delivery systems. For example, the biocompatibility and possible diversity with structures and compositions make them
suitable for a number of targeted delivery applications.

Conventional Stealth
Advantages Drawbacks
Liposomes Liposomes
Enables passive/active Rapid degradation (uptake
targeting by RES(reticuloendothelial
system)
Easy and rapid
internalization Poor scale up/need for
Stimuli extensive modifications
Targeted
Responsive Low immunogenicity
Liposomes Liposomes Short shelf life
Improves solubility/
Polymer bioavailability
Composite Drug protection/
Liposomes Biocompatibility

Liposomes will find more adoption with the development of nanoscale liposomes embedded with drug depot and
polymer depots. Targeted liposomes and environment sensitive liposomes are the ones with maximum potential for
tumors and neurodegenerative disorders, and a number of existing chemotherapeutics are being encapsulated in
stimuli responsive liposomes.
Source: Frost & Sullivan

5
 Technology CapabilityPolymer-Based Carriers

Definition: Polymers have been widely used for sustained release of drugs, and adding functional targeting groups and other
moeties has enabled them to be used as targeted delivery vehicles. A number of natural and synthetic polymers
(degradable/nondegradable, hydrophilic/hydrophobic) with multifunctionalities are being produced for delivering drugs, while
polymer composites with lipids and inorganic nanoparticles are also being developed.

Stimuli Advantages Disadvantages

Multifunctional
Responsive Polymers/ Cell mimicking properties Hypersensitivity (certain
Polymers Co-Polymers (certain polymers) polymers)
Wide range of drugs can Biocompatibility Issues
be loaded (synthetic)
Polymer Artificial Cells Easy Functionalization
Composites
(surface modification)
Controlled Release
Kinetics
Low Cost/Scalable

Polymeric templates have been recently used to develop artificial cells, such as platelets and biomimetic vesicles for
targeted delivery. Use of more natural polymers and polymer conjugated with other delivery methods will witness
increased attention from drug delivery companies and pharmaceutical companies in the next 2 to 3 years.
Source: Frost & Sullivan

6
 Technology CapabilityInorganic Nanoparticles

Definition: Inorganic nanoparticles comprise nanoscale particles made from silica. metals, metal hydroxides, carbon and so
on. A number of multifunctional, inorganic nanoparticles are being developed for targeted drug delivery and imaging
applications. Hybrid drug carriers combining stimuli sensitive hydrogels and inorganic nanoparticles, and conjugation of
biomolecules to nanoparticles are areas of interest.

Carbon Based Gold Based

Particles (AuNPs) Advantages Drawbacks
Optical Properties Toxicity Issues (Long-
Term Safety )
High Stability (over wide
Silica/Alumina temperature and pH Non Biodegradable
Quantum
Nanoparticles range) (accumulation)
Dots
Highly Tunable
Metals/
Oxides/ Evade RES Clearance
Sulfides

Inorganic nanoparticles with multiple functionalities will prompt further research for development of effective cellular
delivery systems. A few gold-based colloids and nanoshells are in clinical trials for cancer applications.
Source: Frost & Sullivan

7
 Technology CapabilityCell-Based Systems

Definition: Cells have been found to act as potential drug delivery agents and they can be used to directly encapsulate the
drug or used with nanoparticles for better pharmacokinetic properties, biocompatibility and higher drug loading capacity. The
figure indicates some of the major types of cell-based delivery platforms in development.

Dendritic Cells/ Advantages Drawbacks

Engineered
Tumor cells
RBCs High Drug Loading Potential Immunogenicity
Capacity (viral, bacterial particles)
Adjuvant Properties for non vaccine delivery

Sustained Release Storage and Formulation

Microbial Ghosts Genetically Issues
and Viral Engineered Stem Biocompatible (except
Particles microbial ghosts) Maintaining integrity
Cells
(RBCs, stem cells,
Scalable/Cost Effective macrophages)

While viruses and virus-like particles (VLPs) have been widely used for vaccine delivery, the use of engineered
bacterial ghosts (BG), engineered RBCs and stem cells is slowly moving to the clinic. Many of these cells and cell
derived-particles are conjugated with other delivery strategies to improve the efficacy of treatment. Stem cell-based
therapies provide a promising approach to the treatment of several diseases in humans, and extensive research on
MSCs for targeted delivery is underway.
Source: Frost & Sullivan

8
 Technology CapabilityMagnetic Particles

Definition: These are micro-and nano-scale particles loaded or conjugated with drugs that get activated when exposed to an
active magnetic field and release drug cargo at the target site. It is a highly controllable and effective form of drug targeting. In
addition to delivery, these particles are apt for safe image guided drug delivery.

Advantages Drawbacks
Evade RES clearance Gradient loss for deep
Image guided delivery seated tissues
with MRI Accumulation of
magnetic material at
Biological Non-Biological Controlled Drug
target site
Release
Requirement for
Highly targeted specialized
Organic Inorganic manufacturing and QC
system

Organic magnetic carriers include magnetoliposomes (ferrofluids entrapped in the liposome core) and polymer
magnetic particles. Iron oxide particles used directly with the drugs are inorganic magnetic particles. Incorporation of
magnetically responsive materials into microspheres makes them susceptible to applied magnetic field, so that they
are concentrated to the target site by the application of a magnetic field externally to that site. Ferriliposomes are
other magnetic particles that could be used in combination with magnetic resonance imaging (MRI) for targeted drug
delivery and also as theranostics. To improve biocompatibility and safety, biological magnetic particles, such as
magnetobiosomes and engineered erythrocytes are being designed, and these are highly promising platforms.

Source: Frost & Sullivan

9
 Technology CapabilityNucleic Acid/Peptide Carriers

Definition: In addition to peptides and nucleic acids being used as effective drugs, they are also being explored for targeting
drugs. Cell penetrating peptides, polypeptide membranes, and DNA Nanorobots are some of the technologies with immense
opportunities. Delivery of siRNA and other nucleic acid drugs, which is still a major challenge can be overcome with the use of
peptide and aptamer-based targeting.

DNA Origami(DNA Peptide Advantages Drawbacks

Nanorobots) Conjugates Highly Targeted Mode of administration
Biocompatible Aptamer Instability
Biodegradable

DNA/RNA Cell Penetrating

Aptamers Peptides

RNA/Peptide dual aptamer systems, polypeptide membranes are being developed for highly targeted delivery and being
extensively researched. DNA Origami is a promising technology area which will enable smart delivery to become a near-term
reality. Overcoming aptamer instability via modifications is improving the clinical value of these systems.
Source: Frost & Sullivan

10
Technology Value Chain

Regulatory
Approval and
Scale Up and Marketing
Large-Scale
Clinical Trials Manufacture
(GMP)
Pre-
formulation
Development and
of Drug Formulation
Conceptualiza Delivery
tion of Drug System
Delivery
Carriers

Source: Frost & Sullivan

11
Key InnovationsTargeted Drug Delivery

Multistage Nanocarriers (Leonardo Biosystems, TX, USA)

Multi-stage nanocarrier-based delivery platform
Customized mesoporous silica nanoparticles are used
Functions better than single-stage systems
For delivering siRNA, small molecule and imaging agents to cancer cells.

Trojan Horse CNS Targeting Technology for Stroke (ArmaGen

Technologies, CA, USA)
The TNF-alpha decoy receptor is engineered as a fusion protein with a BBB
molecular Trojan horse (MTH).
The MTH is an engineered monoclonal antibody (MAb) against the BBB
specific transferrin receptor (TfR).
Facilitates receptor mediated transport of the drug across the BBB. Blood
Brain
Ensures effective and safe delivery of drugs to the brain.
Barrier

Thermally Responsive Liposomes, Lysolipid Thermally Sensitive Liposomes

(LTSL) (Celsion Corporation, NJ, USA)
A patented liposomal tumor targeting delivery system
Delivers high concentrations of drug to target site (tumors) on exposure to local
Hyperthermia
hypothermia.
Currently carrying out Phase 3 clinical trials (HEAT Study) for its lead candidate Drug release
ThermoDox, a formulation of doxorubicin for targeting HCC (hepatocellular into tumor
carcinoma).
Expanded applications to develop formulations for other chemotherapeutics,
such as docetaxel and carboplatin.
Source: Frost & Sullivan

12
 Key InnovationsTargeted Drug Delivery (continued)

IVECT Method , (Intezyne, Inc, FL, USA)

A multidisciplinary approach of drug delivery that has the potential to revolutionize cancer
treatment.
Developed proprietary polymeric micelles that deliver drugs to tumors using a triggered
release mechanism.
It is a highly tunable and cost-effective platform that can incorporate different targeting
ligands.
Currently has four cancer chemotherapeutics in its pipeline: two lead programs in final
preparation for IND submission and two others in earlier stages of preclinical development.

Resealed Erythrocytes for targeted and Controlled Dryg delivery, Erydex (Erydel Spa,
Italy)
An erythrocyte based drug delivery system for sustained release of drugs
Encapsulaties autologous red blood cells with glucocorticoid analoguedexamethasone
sodium phosphate (Dex 21-P).
Used for treatment of chronic disorders such as cystic fibrosis, Ataxia Telangiectasia.
Ventured in to diagnostics and targeted drug delivery (EryTargeting) aimed at delivery of drug
cargo only to targeted macrophages.

Resealed RBCs for Targeted Drug Delivery to Tumors , GRASPA (ERYTech Pharma,
France)
A tumor targeting therapeutic utilizing erythrocyte encapsulation technology.
Encapsulates a wide array of molecules such as peptides, proteins and small molecules for
delivery.
Targets the tumor microenvironment using the encapsulated L-asparginase which depletes
the circulating asparagine, a tumor growth factor thereby starving the tumor cells to death.
Currently tested in Acute Lumphoblastic Leukemia, Pancreatic cancer and Acute Myelod
Leukemia.
Source: Frost & Sullivan

13
Targeted Drug Delivery SystemsDrivers and Challenges

Need for effective delivery of biologics

Patenting opportunities for targeted therapies
Quicker time to market/ease of approval
Discovery of disease biomarkers
Development of spatially/temporally controlled systems
Advances in Nanotechnology
Improve patient compliance

Competition from medical devices for targeting

High costs of several types of systems
Potential long-term effects of nano particles
Lack of multipronged/ combinatorial targeting approaches
Poor funding scenario

Source: Frost & Sullivan

14
Technology Development Lipid Based Carriers
Below listed are some of the areas being developed by universities and research institutions
Dual response sensitive liposomes
Self assembling nanoemulsions
Zwitterionic oligopeptide liposomes targeting mitochondria
Liposomes fused on inorganic nanoparticles
Targeted liposomes for intracellular delivery
Company
Silence Therapeutics (UK)
Celsion Corporation(NJ, USA)
LiPlasome Pharma ApS (Denmark)
2 3
1 4
4.0
0 5
Technology Development
Key
0-2 Less than 10 company
developments
2 - 3.5 Between 10 and 20 company
developments
3.5 - 5 More than 20 company
developments
Key Developments
Silence's siRNA delivery platform is based on the proprietary lipid moeities that
embed siRNA into lipid-bi-layer particles. The siRNA is combined with Silence's
developed lipid moieties containing cationic lipids, co-lipids and PEGylated lipids to
form nanoscale structures.
ThermoDox, the patented heat sensitive liposomal formulation of doxorubicin is in
clinical trials for liver cancer and also being tested for a number of oncology
indications.
The tumor targeting drug loaded lipid nanocarriers are designed to be susceptible to
degradation by phospholipase A2 (PLA2), which is high in the cancer environment.
The prodrug lipids are degraded by PLA2 and get converted to
active drugs such as anticancer lysolipids and/or fatty acid drug derivatives. The
degraded entities also enhance the permeability of the drugs across cancer cell
membranes to deliver high doses of drug to the target site.
Source: Frost & Sullivan
15
Technology DevelopmentPolymer Based Carriers

Below listed are some of the areas being developed by universities and research institutions 2 3

Artificial Cells, Synthetic Platelets (Scripps Research Institute and Sanford-Burnham Institute) 1 4
Dual Stimuli Responsive Smart Capsules (University of Melbourne)
Protein Polymer Drug Conjugates 4.5
Polymer drug depot in liposomal nanoparticles 0 5
Technology Development
Multifunctional polymeric vesicles
Stealth particles coated polymers, Amphiphilic Biodegradable Dendrimer-Like Star Polymers

Company Key Developments

Flexible polymer platform for targeted, sustained delivery of biopharmaceuticals.
GlycoPol TM is a targeting glycopolymer developed by attachment of saccharides a
PolyTherics Limited (UK)
poly(methacrylate) backbone. Drugs can be attached to the backbone for targeted
delivery.
IVECT Copolymer Micelles that are based on the IVECT Method offer a lost cost,
modular and highly targeted delivery platform. It is highly tunable and can be used to
deliver a number of drugs for varied indications.
Intezyne, Inc. (FL, USA) The lead candidate IT-141, has demonstrated significant activity against a diverse
number of cancer cell lines. Another formulation IT-143, is the encapsulated
daunorubicin, is being assessed for treatment of lung cancer, osteosarcoma, and
ovarian cancer.
The company has a portfolio of in house developed and acquired targeted delivery
Arrowhead Research Corporation (CA, USA) platforms, of which DPCs(Dynamic polyconjugates) and RONDEL are based on
polymer nanoparticles. Both are being explored for delivery of siRNA therapeutics.

Source: Frost & Sullivan

16
Technology Development Inorganic Nanoparticles

2 3
The adoption of inorganic nanoparticles is on the rise with the development of gold and silica
nanoshells, nanowires, nanorods, and many more. They are emerging as an important and useful 1 4
class of targeted entities that can be functionalized for specific needs. These inorganic nanoparticles 3.5
can also be used for simultaneous imaging and delivery applications. Iron oxide, silica, gold,
0 5
fullerenes, and carbon are the most widely researched materials. Technology Development

Below listed are some of the areas being developed by universities and research institutions

Mesoporous nanoparticles conjugated with peptides, antibodies, and other entities

Stimuli sensitive nanoparticles
Surfactant functionalized nanoparticles
Aptamer gated nanoparticles
Multistage nanoparticles

Company Key Developments

Multistage mesoporous silica nanoparticle based platform for spatio-
temporally controlled drug release is attracting a lot of interest from investors
Leonardo Biosystems (TX, USA) and pharma companies. The system is undergoing optimization and
enhancements.

The technology is based on pegylated colloidal gold nanoparticles that can be

CytImmune Sciences Inc. used directly as drugs via tumor targeting molecules or can be used as
carriers for cancer drugs.
Source: Frost & Sullivan

17
 Technology Development Cell Based Carriers
2 3
The adoption of cell-based drug carriers is relatively low despite research being carried out for more
than a decade. Modified RBCs form the majority of therapeutic carriers, while stem-cell based drug 1 4
targeting is showing promising results in clinical trials. Microbial cells have been used for targeting
2.5
vaccines and drugs for several years, and modified forms of these cells are now being developed for
0 5
more effective and safe targeting. Technology Development

Below listed are some of the areas being developed by universities and research institutions

Resealed erythrocytes/ Engineered erythrocytes with viral fusion proteins (for example, Erythro-magneto-HA virosomes)
Engineered mesenchymal/ neural stem cells (for example, Silica nanorattle-drug anchored mesenchymal stem cells
Virosomes/Bacterial ghosts for DNA vaccine and subunit vaccines
iPSCs reprogrammed for organelle specific targeting
Magnetotactic bacteria
Prodrugs/Drugs bound to RBCs in circulation for long-term thrombosis treatment

Company Key Developments

Erythrocyte loaded drugs for multiple disease areas currently in clinical
EryDel SpA (Italy), EryTech Pharma (France)
development. These are being used for controlled delivery as well as targeting.
Proprietary virosome-based platform for targeted drug delivery and adjuvant
activity for subunit vaccines. A number of vaccines are in advanced phases of
Pevion Biotech AG (Germany)
clinical trials using their VLP technology, and has also been outlicensed to
several pharma majors.
EDV (Engene Delivery Vehicle) technology basically consists of inert bacterial
cell derived nanoscale minicells conjugated with bispecific antibodies for highly
Engene IC (Australia) targeted intracellular delivery of cancer drugs/siRNA. Immune stimulating
properties enhance performance and the drugs using this platform are currently
in clinical trials.
Source: Frost & Sullivan

18
 Technology DevelopmentMagnetic Particles

Below listed are some of the areas being developed by universities and research institutions 2 3

Bacterial magnetosomes from magnetotactic bacteria for drug targeting that can be functionally superior 1 4
to artificial magnetic particles
Ocular magnetic drug targeting
Magnetic resealed erythrocytes 1.5
Enzyme and temperature responsive magnetic nanoparticles 0 5
Technology Development
Multifunctional nanoparticles for delivery and imaging (for example, multilayered nanorattles)

Company Key Developments

Biodegradable, magnetic drug-loaded particles in combination with a magnetic

Vascular Magnetics, Inc, (PA, USA) targeting catheter and a magnetic field generating device that guides the
particles to narrowed arteries in PAD (Peripheral Artery Disease).

Magnetic vectored drug delivery using magnetically responsive therapeutic

Nanobiomagnetics Inc. (SW R and D) (OK,USA)
constructs.

Magnetic transfection method MagnetofectionTM using DNA, siRNA coupled

nanoTherics (UK) with magnetic nanoparticles to form a complex. Upon exposure to oscillating
magnetic arrays, cells show uptake of the complex via rapid endocytosis.

Iron oxide nanoparticles with aminosilane coating that safely delivers drugs to
MagForce AG ( Berlin, Germany)
tumors upon activation by their proprietary NanoActivator magnetic field.

Source: Frost & Sullivan

19
Technology Development Aptamers/Peptides/Nucleic
Acids
2 3
Below listed are some of the areas being developed by universities and research institutions
1 4
Peptide Dendrimer Conjugates
2.5
Engineered OleosinSelf assembled to form Biomimetic Vesicles (University of Pennsylania)
5
Peptide and Aptamer Functionalized Nanoparticles; Aptamer nanoparticle Bioconjugates 0
Technology Development
(PANOPTES project --novel peptide-based nanomaterials for ocular delivery)
Cell penetrating peptides (HIV TAT peptide, human calcitonin (hCT) hormone)
Carbohydrate mimetic peptides (UC, Berkeley)
Cell specific aptamers, peptide conjugated environment sensitive particles

Company Key Developments

Condensed nanoparticles of cell penetrating peptides and RNA
Savara Inc. (TX, USA) therapeutics for targeted intracellular delivery. This is known as
Nanonucleic technology used primarily for RNAi therapy.

Layer by layer assembly of polypeptide artificial biofilm nanoparticles for

developing synthetic vaccines. The synthetic nanoparticles incorporate
Artificial Cell Technologies, Inc (CT, USA)
immunogenic epitopes and give rise to Artificial Virus like structures
that can be used for vaccine delivery.

Aptabodies developed by the company are proprietary, functionalized

aptamers that can be used for drug delivery or diagnostics. The
Aptagen, LLC (PA, USA)
company is a good collaborative partner for pharma/biotech companies
for delivery of peptide therapeutics.

Source: Frost & Sullivan

20
Life Cycle Analysis of Drug Delivery Systems
Market Position

Conventional Liposomes
Non Biodegradable Polymers

Stimuli sensitive Stimuli responsive

liposomes polymers
Conjugates/Hybrid Carriers/
Composite particles

Engineered peptides/Aptamers
Magnetic nanoparticles

Functionalized Polymersomes
Multistage/Multifunctional
nanoparticles Inorganic nanorods, nanoshells,
nanowires
Biological Magnetic
carriers Stem cell carriers
Artificial cells/
Biomimetic particles DNA Nanorobots
Time
Development Growth Maturity Decline

Source: Frost & Sullivan

21
Demand Side Analysis

Applications
Versatility

Smart
Delivery Tunability

End-User
Requirements

Cost Market
Effectiveness Exclusivity
and Scalability

Biocompatibilit
y

Source: Frost & Sullivan

22
Potential Applications - Ocular

Quark
InSite Vision Inc. Integral BioSystems
Pharmaceuticals

Novagali Pharma Ocular Therapeutix

Challenges with regard to topical administration include poor access to the posterior portion of the eye,
need for frequent doses, and poor controlled delivery.
Ophthalmic inserts developed for sustained release suffer from limitations, such as high costs and difficulty
with insertion.
Liposomes and polymers - most widely used vehicles for ophthalmologic delivery. Targeting ligands that
can cross the Blood Retinal Barrier(BRB) explored for a number of orphan retinal diseases.
Identification of ocular transporters and development of transporter targeted drugs modified with targeting
ligands
Other commonly deployed delivery systems - functionalized nanoparticles, in situ forming gels, and
colloidal dosage forms

Source: Frost & Sullivan

23
Potential Applications - CNS

Serina Therapeutics Inc. ArmaGen Technologies Lauren Sciences LLC

Advectus Life
to-BBB VECT-HORUS Angiochem Inc.
Sciences Inc.

Systemically administered drugs have limited access across the BBB, while local administration is painful
and challenging.
Most innovative drug developments for neurological disorders are biologicals, such as cell based therapy,
RNAi or gene therapy.
Drug delivery systems that can cross the BBB (blood brain barriers) primarily include nanoparticles with
targeting ligands and CNS targeting vectors that can bind to receptors on the BBB and cross the barrier in
order to improve efficacy and increase safe therapeutic window.
Most of the research is in the basic research or pre-clinical stage
A number of partnerships and collaborations have been witnessed in the last 1 to 2 years. (For example,
Genzyme Pharmaceuticals and Pharmidex Pharmaceutical Services Ltd)

Source: Frost & Sullivan

24
Potential Applications - Oncology

Celsion Corp BIND Biosciences LiPlasome Pharma

Savara Silence CytImmune

Alchemia
Pharmaceuticals Therapeutics Sciences Inc.

Intezyne EnGene IC ERYTECH Pharma Cerulean Pharma Inc.

MagForce AG

Oncology is the most well penetrated area - more than 80% of targeted drug delivery activity is focused on
safe and effective delivery of chemotherapeutics to cancerous cells.
Strategies based on differences in tumor cell metabolism, tumor microenvironment, and expression of
receptors on tumor cell surfaces are being developed.
Most of them in clinical development are conjugates of polymers, liposomes, and inorganic nanoparticles,
while magnetic targeting and imaging is also being explored by a few Participants.
Cell-based delivery systems that can trigger the immune system against cancer cells and multifunctional,
multiple ligand targeting strategies will take predominance.
Source: Frost & Sullivan

25
Potential Applications Infectious Diseases

Artificial Cell Arrowhead Research

EryDel
Technologies Inc. Corporation

Xenetic Biosciences Pevion Biotech AG

High degree of noncompliance to therapy in a number of infectious diseases - led to development of

targeted drugs that can specifically target the pathogen and associated pathways.
TB, HIV, and malaria are some of the highly researched areas.
Virosomes and bacterial ghosts have been widely used for vaccine delivery.
By developing different nanoparticle formulations with cell penetrating peptide conjugates, glycomimetic
peptides, and other moieties, intracellular delivery to pathogens is becoming possible.

Source: Frost & Sullivan

26
Potential Applications Cardiovascular

Vascular Magnetics Inc. Spheringenics Inc. BIND Biosciences

Eluting stents and cardiovascular implants invasive drug delivery methods strong need for non-invasive
drug delivery systems.
Targeted immunoliposomes and biodegradable targeted polymeric particles are being developed for
cardiac delivery and imaging.
Cell-selective targeted drug delivery - key research area for cardiovascular applications.
In atherosclerosis and other ischemic conditions, it is necessary to develop systems that can release drugs
on sensing difference in shear stress or tissue injury.

Source: Frost & Sullivan

27
Potential Applications Pulmonary

BioParticle
MannKind Corporation Liquidia Technologies
Technologies

Pulmatrix Insmed Inc.

Most appropriate route for the treatment of asthma, cystic fibrosis and other pulmonary diseases such as
tuberculosis, COPD, and lung cancer; explored for systemic diseases like diabetes.
Useful for developing inhalable vaccines, which hold huge market potential as a needle-free vaccination
strategy for a number of respiratory infections.
Peptide and protein drugs are ideal for pulmonary delivery as they undergo degradation in the
gastrointestinal (GI) tract).
Liquidias PRINT (Particle Replication In Non-Wetting Templates) and MannKinds Technosphere have
demonstrated success for pulmonary delivery.
Liposomes are the most extensively studied system for controlled drug delivery to the lungs.
Emerging areas of interest are magnetic aerosol droplets, bioresponsive nanoparticles, and co-polymers
with better release profiles.
Source: Frost & Sullivan

28
Potential ApplicationsMapping

Disease prevalence and Company

Funding Research Initiatives
criticality of delivery challenges Developments
Cardiovascular Medium Medium Medium Low

Ocular Medium Medium Low Low

CNS High Medium Medium Medium

Oncology High High High High

Infectious Diseases
Medium Low Low Low
(Targeting Pathogens)

Pulmonary High High Medium Medium

Criteria

Key - Funding Key Research Initiatives Key Company Developments

Low Less than $100 million
federal and private funding
Medium Between $100 - $200
million federal and private
funding
High More than $200 million
federal and private funding
Low Less than 50 published
research projects by
academia
Medium Between 50 and 100
published research projects
by academia
High More than 100 published
research projects by
academia
Low Less than 10 companies
working on TDD
Medium Between 10 and 30
companies working on TDD
3.5 - 5 More than 30 companies
working on TDD

Source: Frost & Sullivan

29
Assignee-wise Patent Distribution

Total Number of Patents/applications 1080 (100 unique patent families). Source: Frost & Sullivan

30
Top Countries for Publishing Patent Applications

US = United States
EP = European Union
WO = WIPO
AU = Australia
CA = Canada
JP = Japan
CN = China
AT = Austria
DE = Germany
ES = Spain

Most of the innovations in targeted drug delivery is happening in the US and European Union, which is clearly indicated by the number of patent
applications published from these regions.
Source: Frost & Sullivan

31
Patent Publishing Trends

This chart shows the patenting trends in the last 4 years and the patenting trend has been quite stable. On an average 250 patents were published
every year. Source: Frost & Sullivan

32
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PerspectiveTM from which to drive decision making. Technical, Econometric, Application, and Market
information ensures that clients have a comprehensive view of industries, markets, and technology.

Real-time intelligence on technology, including emerging technologies, new

Technical R&D breakthroughs, technology forecasting, impact analysis, groundbreaking
research, and licensing opportunities.
In-depth qualitative and quantitative research focused on timely and critical
Econometric global, regional, and country-specific trends, including the political,
demographic, and socioeconomic landscapes.
Insightful strategies, networking opportunities, and best practices that can be
applied for enhanced market growth; interactions between the client, peers,
Application and Frost & Sullivan representatives that result in added value and
effectiveness.

Global and regional market analysis, including drivers and restraints, market
Market trends, regulatory changes, competitive insights, growth forecasts, industry
challenges, strategic recommendations, and end-user perspectives.

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