Global Nanopharmaceutical Drugs Market is Expected to Reach $79.

29 Billion by 2026

The global nanopharmaceutical drugs market is anticipated to grow over $79.29 billion by
2026. The growth of the market is aided by the remarkable growth in the liposome and
polymer drug delivery systems.
Technological advancements in the healthcare industry have always played a crucial role in
its development. Among the innumerable advancements witnessed by the industry,
nanopharmaceuticals can provide rapid and sensitive detection of cancer-related targets,
enabling scientists to detect molecular changes even when they occur only in a small
percentage of cells. Nanotechnology when clubbed with healthcare has the potential to
generate unique and highly effective therapeutic products. The recent advancements in the
pharmaceutical industry, such as drug delivery at nano and microscopic level, investment in
precision medicine, advancement in regenerative medicine, and genomic technologies, have
led to big breakthroughs in the field of pharmaceutical research. Nanopharmaceutical
provides new and promising pathways to combat genetic diseases and reduce the overall
global economic burden.
The major factors driving the growth of this market, are government and private funding to
support the development of regenerative medicine, rising prevalence of chronic diseases and
genetic disorders, increase in the global healthcare expenditure, and rapid growth in the aging
population.
BIS Research Report
Nanobiotechnology is a biological system invented at the molecular level and has helped in
the development of pharmaceutical delivery devices. The delivery of conventional
pharmaceuticals or substances such as peptides, recombinant proteins, vaccines and
nucleotides are combined to nanoparticles such as micelles, liposomes, solid lipid
nanoparticles, polymeric nanoparticles, functionalized nanoparticles, nanocrystals,
cyclodextrins, dendrimers, nanotubes and metallic nanoparticles for site specific drug
delivery. Significant progress has been made in the field of nanobiotechnology, resulting in
the emergence of a huge number of medical products. By the end of 2020, one-third of
research patents and many start-up companies in the nanomedicine are expected to engage in
the applications of nanotechnology.
According to Abdul Wahid Analyst at BIS Research, "In 2017, North America was the
leading contributor to the market with 51.8% of the market share in terms of revenue.
Polymer drug carrier systems and liposome drug carrier systems are the two sub-segments
that are expected to progress at significant rates, during the forecast period. Further, the
significant development in the reimbursement policies, government regulations in the region
are also expected to fuel the growth of the North America nanopharmaceutical drugs market.
Research Highlights:
 The penetration of the nanodrugs within the next 6-7 years is expected to give rise to a
new era of the pharmaceutical market and the use of nanotechnology for a variety of
medicine areas is expected to increase with a focus on targeted drug delivery systems
and novel therapeutics
  Currently, the polymer drug carrier in the nanotechnology drug delivery market is the
major contributor to the global nanopharmaceutical drugs.
 Several large pharmaceutical companies and small-medium enterprises are the
significant contributors of the market.
 Factors such as rising prevalence of chronic diseases, growth of the biologics market,
new product launches, drug innovation and technological advancements are driving
the growth of the nanopharmaceutical market in North America.

Abstract

Pharmaceutical nanotechnology has generated breakthrough developments in improving

health care and human life from its emergence. The biomaterials employed mainly aim at
improving drug delivery systems, imaging and diagnostic technologies while the nanoscale
materials are in widespread use in other industries such as electronics and optics. Such
advancement may revolutionize the drug development and therapy with new and more
efficient treatments. Although, nanotechnology assists humankind in improving its well
being, it has certain limitations that entail thorough investigation by the regulatory and
scientific authorities. To address concerns regarding the safety and toxicity profile of the
nanopharmaceuticals, we have reviewed the challenges and solutions of nanopharmaceuticals
use in human health and the related health risks. The regulatory authorities may enforce the
nanopharmaceutical industries to conduct comprehensive toxicity tests and monitor the
adverse drug reaction reports in close collaboration with the scientific community to act
accordingly and inform the public as the implementation of the strategy.

Graphical abstract

Nanopharmaceuticals have tremendous potential for human use as therapeutic or diagnostic

agents. But their toxicity profile should be well addressed and the respective regulatory
framework developed and reinforced by the authorities.
Introduction

Pharmaceutical nanotechnology deals with the scope of pharmaceutical compounds that

emerge from a multidisciplinary field of science entailing the development and application
of molecular structures with dimensions smaller than 100 nm. The nanoscale feature of
these products and devices render them special capabilities that can be used to produce
devices and products as therapeutic agents and other purposes . Pharmaceutical
nanotechnology has generated breakthrough developments in health care and human life ,.
The biomaterials employed in this field mainly aim at improving drug delivery systems,
imaging and diagnostic technologies while the nanoscale materials are of widespread use in
other industries such as electronics and optics . However, nanotechnology applications in
the treatment of some of most critical metabolic and genetic diseases and cancer, delivery
systems, genetic tests, as well as imaging and diagnostics are promising enough to absorb
huge amounts of investment into research and development efforts both in the academia
and the industry . Noteworthy, nanotechnology provides humankind with exceptional
opportunities to improve its wellbeing, but it also has certain limitations that entail
thorough investigation by the regulatory and scientific authorities . Concerns about human
use of nanomaterials become overwhelming when we know that these nanostructures do not
completely abide by the scientific principles that form the basis for our knowledge about
how human physiologic system deals with exogenous compounds and toxicity tests also fail
 to adequately address the nanotoxicity issues for human beings, animals and the
environment.

With all the features in mind, there are certain concerns with regards to nanoparticulate
structure for human use [13]. Nanoparticles toxicity has attracted the most vital criticism
because they represent exceptional characteristics such as size, size distribution, surface
charge and properties, expanded surface area, self-assembly and stability [4].

These features influence the nanoparticles’ ADME (Adsorption, Distribution, Metabolism

and Excretion) properties like cellular uptake, distribution within the body fluids, and
transport through biological barriers. For instance, the tiny molecular size of the
nanoparticles enables them to cross the natural biological barriers in the brain and eye or
other cells. However, our knowledge is yet scant enough not to be sure about the
mechanistic toxicology of nanoparticles since the currently available toxicity tests are not
fully assuring and data obtained from in vitro or animal studies are not always
extrapolatable to human .

Exposure to nanopharmaceuticals may affect manufacturing personnel, healthcare

professionals and the patients. However, when the nanopharmaceuticals are disposed or
excreted via waste water, the general public will also be at exposure. Therefore, elaborate
monitoring systems based on physicochemical characterization are required [1, 15]. As the
nanoparticles enter the body, they penetrate the epithelial and endothelial barriers and then
undergo cellular uptake processes like diffusion, different endocytosis pathways such as
receptor mediated endocytosis dictated by their physicochemical and surface properties.
Then their biodistribution also follows relatively unknown patterns rather than those of
other conventional pharmaceuticals, though such organ deposition in the Central Nervous
System (CNS) and growing fetus would be of dramatic concern along with other organs
like liver, kidney and spleen. Cytotoxicity and genotoxicity have been seen with nanodrugs
containing metallic ions like aluminum oxide, gold, copper oxide, silver, zinc oxide,
titanium oxide, iron oxide and carbon based nanomaterials. Although silica and polymer
based nanomaterials have been deemed to be more biocompatible and relatively nontoxic,
they may also involve ROS formation and cytotoxicity [9]. Some toxicity tests have been
proposed for the nanopharmaceuticals before their approval both in vitro and in vivo.

Regulatory framework for nanopharmaceuticals

Nevertheless, the authority continues to run post-market monitoring surveys to protect the
consumers while maintaining its role in preparing technical documents and advisory
guidelines [21]. The bioequivalent versions of the nanotechnology derived products or
nanosimilars compose a new era of extensive regulatory burden. In addition, regulatory
authorities of other countries have to keep in pace with the market trend and mobilize their
capacities for the oncoming nanosimilars. Overall, the nanoparticulate biomaterials such as
liposomes and dendrimers involve more elaborate investigations caused by their modified
formulations and ADME [3, 22].

Nanopharmaceuticals approval should contain close characterization of physicochemical

properties as they have size and size distribution that may increase the chance of
thromboembolic complications via facilitating the thrombosis cascade. On the other hand,
nanopharmaceuticals require sophisticated stability and ADME studies because most of the
critical parameters of their safety and efficacy may evade during shelf life and cause
 morbidities and fatalities. Moreover, FDA has approved some liposomal, dendrimer based,
PEGylated and albumin bound compounds while the overwhelming number of candidates
are on their way to market .

It should not be forgotten that discovery of new medicines has been always expensive,
time-consuming, competitive, with unknown outcome to pass all preclinical and clinical
phases of approval. Therefore, to reduce the attrition rate in further steps, investigators
must pay enough attention to safety of medicines, development risks, dose ranging, early
proof of concept/principle, and patient stratification based on biologically and/or clinically
validated biomarkers [27].

Future prospects of nanopharmaceuticals in human health

With the advent of nanosized structures and their special characteristics, many fields of
science started to take advantage of these extraordinarily modifiable and functional features
based on their special needs. Medical and pharmaceutical experts also employed these
capabilities to develop new drugs, medical devices and therapeutic methods. Cancer is a
major cause of mortality and morbidity that has benefited from nanopharmaceuticals and
promising progress is also on the way. In spite of the currently approved drugs for cancer
chemotherapy, there are more than twenty candidates in clinical trials for approval process.
These candidates either improve therapeutic/toxicity profile of existing drugs or contain
novel molecules [28, 29]. Dermatology is also applying nanostructures for different
diseases treatment because of the special structure of skin and natural barriers that could be
simply overcome through noninvasive methods using the nanosized structures [30]. Drug
delivery system, nanotherapeutics, nanobots, nanoshells, nanotubes, gene therapy, and
vaccination and immunization improvement rank among the functional structures that
pharmaceuticals will borrow from nanotechnology while chip technology, quantum dots
and sensor nanobots emerge advantageous for diagnostic purposes [31, 32]. However,
reconstructive medicine and tissue engineering look forward to applying nanotechnology to
cover the gap in clinical practice by providing biodegradable and biocompatible tissues
[33]. Radiation enhancers are also under investigation to increase the usability of
radiotherapy in war against cancer [34]. Personalized medicine is the other field of
interdisciplinary medical science that is enjoying the nanomaterials like theranostics and
data management to improve patient care based on certain patient’s needs, genetic and
health status [35].

Concluding remarks

In conclusion, it should be stated that nanopharmaceuticals may pave the way for new
therapies for unmet medical needs and optimization of the existing therapies with their
promising features. But, in the meanwhile their limitations should also be considered since
adverse events may come out during their use in the populations with metabolic variations
as well as health status. The nanodrugs modified biokinetics necessitate well established
toxicology profiling through in vitro and especially in vivo tests since the lab tests mostly
cover their toxicity in cell lines with different physiological properties rather than the
healthy people and patients. The test endpoints may include oxidative stress burden,
inflammatory system, genotoxicity, carcinogenicity, respiratory, cardiovascular, central and
peripheral nervous system, hematopoietic and lymphatic system, developmental and
reproductive toxicity. To achieve this goal, validated and standard test protocols as well as
reference standards seem critical. Therefore, it would be advisable for the regulatory
authorities to enforce the nanopharmaceutical industries to conduct comprehensive toxicity
tests and monitor the adverse drug reaction reports closely to act accordingly and inform
the public. Proper collection of possible toxicities and adverse events from the medical and
public community is recommended.

Materials can exhibit new or altered physicochemical properties at nanoscale dimensions,

which can enable the development of novel products. The very changes in biological,
chemical and other properties that can make nanotechnology applications so exciting,
however, also may merit examination to determine any effects on product safety,
effectiveness, or other attributes.

The application of nanotechnology may result in product attributes that differ from those of
conventionally-manufactured products, and thus evaluations of safety or effectiveness of
FDA-regulated products that include nanomaterials or otherwise involve the application of
nanotechnology should consider the unique properties and behaviors that nanomaterials may
exhibit. However, FDA does not categorically judge all products containing nanomaterials or
otherwise involving the application of nanotechnology as intrinsically benign or
harmful. FDA will regulate nanotechnology products under existing statutory authorities, in
accordance with the specific legal standards applicable to each type of product under its
jurisdiction.

According to Coherent Market Insights, the global nanopharmaceuticals market

was valued at US$ 28,434.3 million in 2017, and is projected to exhibit a CAGR

of 22.1% over the forecast period (2018 – 2026).

Key Trends and Analysis of the Nanopharmaceuticals Market:

Various advantages of nanopharmaceuticals over other medicines such as faster drug

delivery and higher efficiency, increase in research and development activities for
discovery of new products for precision medicine, cardiovascular, and other diseases,
technological advancements in regenerative medicine, and high prevalence of neurological
disorders and cancer are some of the factors that will increase growth of the
nanopharmaceuticals market.

Furthermore, key players operating in the market are focused on adopting

various business strategies such as acquisition strategies in order to gain

access to innovative products and expand its product offerings in the

potential market.
 * The nanopharmaceuticals market is expected to exhibit a CAGR of 22.1%

during the forecast period (2018 – 2026). This growth is attributed to

increasing incidences of cardiovascular diseases, cancer, and infectious

diseases, and advantages of nanopharmaceuticals over macroscopic level of

medicines. According to the World Health Organization (WHO) Factsheet

November 2016, estimated around 16% of all deaths of children below 5

years in 2015 were due to Pneumonia.

* Market growth is attributed to rising approvals and launches of novel

products for treatment in neurological disorders. For instance, in August

2009, Janssen Pharmaceuticals, Inc. received U.S. Food and Drug

Administration (FDA) approval for Invega Sustenna used in treatment of

schizophrenia in adults.

* Key players in the market are focused on adopting mergers and acquisitions

strategies to enhance its product portfolio, which in turn is expected to

propel the market growth over the forecast period. For instance, in 2017,

Gilead Sciences acquired Kite Pharma.

NANOTECHNOLOGY MARKET – Nanotechnology Markets in Healthcare &

Medicine

INTRODUCTION
In the field of nanomedicine research, the US accounts for one-third of all publications and
half of patent filings. A comparison between Europe as a whole and the US shows that while
Europe is at the forefront of research, the US leads in the number of patent filings. The strong
patenting activity of US scientists and companies indicates a more advanced
commercialization status.

According to BCC Research (www.bccresearch.com), the global market for nanoparticles in

the life sciences is estimated at over $29.6 billion for 2014. This market is forecast to grow to
more than $79.8 billion by 2019, to register a healthy compound annual growth rate (CAGR)
of 22%. The biggest increase will come in the area of drug delivery systems.

As products complete clinical trials and gain US FDA market approval, the revenues from
these products will grow at 23%. Basic biotechnology research revenues will increase due to
the quest to find more nanoparticle applications, as more drugs become successfully
delivered by these carrier systems. Drug development and formulation will show steady
sustained growth at 20.7%. Nanoparticles for use in diagnostic imaging will continue to show
healthy growth at 20.1%. This will result from the need to develop more definitive
nanoparticle markets for disease diagnosis.

APPLICATIONS IN MEDICINE

Nanomedicine includes several distinct application areas, including drug delivery, drugs and
therapies, in vivo imaging, in vitro diagnostics, biomaterials, and active implants. In
these fields, nanomedicine has seen increased research activity during the past
decade. Currently, nanomedicine accounts for about 5% of nanotechnology
research publications worldwide.

The dominant research field in nanomedicine is drug delivery, contributing 76% of the
scientific publications, followed by in vitro diagnostics with a contribution of 11%. The
countries of the European Union account for 36% of all nanomedicine publications
worldwide, compared to the US with a contribution of 32% and Asia with 18%. Research
efforts in nanomedicine are driven by significant governmental nanotechnology funding
programs. Three countries – the US, Germany, and Japan – have given clear commitments to
nanomedicine by establishing focused nanomedicine research programs.

However, when one looks at the commercialization of this field, the US emerges as having
about half of the world market for nanomedicine products. US companies manufacture 45%
to 50% of marketed nanomedicine products, while European companies have a 35% share.
Product pipelines suggest that this gap will widen, reflecting mainly the weak position of
European nanomedicine companies in the drug delivery sector, where they represent less than
one quarter of all the companies in this field, compared to 60% for US companies.
Of the approximately 200 companies identified as active in nanomedicine worldwide, some
three-quarters are startups and SMEs focusing on the development of nanotechnology-
enhanced pharmaceuticals and medical devices. Another 40-plus major pharmaceutical and
medical device corporations have nanomedicine products. Individual nanomedicine
application areas are defined below.

Drug Delivery: Nanoscale particles/molecules are developed to improve the bioavailability

and pharmacokinetics of therapeutics. Examples are liposomes (and virosomes), polymer
nanoparticles, nanosuspensions, and polymer therapeutics. Drugs in which a protein is
combined with a polymer nanoparticle or chemical nanostructure to improve its
pharmacokinetic properties would qualify as nano-enhanced drug delivery.

Drugs and Therapy: Nanoscale particles/molecules used in the treatment of diseases that
according to their structure have unique medical effects and as such differ from traditional
small-molecule drugs; examples include drugs based on fullerenes or dendrimers.

In Vivo Imaging: Nanoparticle contrast agents, particularly for MRI and ultrasound, provide
improved contrast and favorable biodistribution; for example, superparamagnetic iron oxide
nanoparticles for use as MRI contrast agents.

In Vitro Diagnostics: Novel sensor concepts are based on nanotubes, nanowires, cantilevers,
or atomic force microscopy applied to diagnostic devices/sensors. The aim of these sensors is
to improve sensitivity, reduce production costs, or measure novel analytes (eg, Alzheimer
plaques) that could not otherwise be detected reliably.

Biomaterials: These include self-assembling particles or other types of nanomaterial that

improve the mechanical properties and biocompatibility of biomaterials for medical implants;
examples include nanocomposite materials used as dental fillers and nanohydroxyapatite used
for implant coatings and bone substitutes.

Active Implants: Particles/materials improve electrode surfaces and biocompatibility of

device housings. Examples include magnetic nanoparticle-based coatings that make medical
implants safe for use with MRI imaging.

NANOMEDICINE MARKET

Nano-enabled medical products began appearing on the market over a decade ago and some
have become best-sellers in their therapeutic categories. The main areas in which
nanomedical products have made an impact are cancer, CNS diseases, cardiovascular disease,
and infection control.

At present, cancer is one of the largest therapeutic areas in which nano-enabled products have
made major contributions; these include Abraxane, Depocyt, Oncospar, Doxil, and Neulasta.
Cancer is a prime focus for nanopharmaceutical R&D, and companies with clinical-stage
developments in this field include Celgene, Access, Camurus, and Cytimmune.

Treatments for CNS disorders including Alzheimer’s disease and stroke also
feature prominently in nanotherapeutic research, seeking to build on achievements
already posted by products such as Tysabri, Copazone, and Diprivan. According to BCC
Research, this is a field hungry for successful therapeutic advances and annual growth
from existing and advanced pipeline products is expected to reach 16% over the next 5 years.

The US market is by far the largest in the global nanomedicine market, and is set to continue
to dominate the world marketplace, but other national markets are expected to increase their
shares over the next 5 years.
COMMERCIALIZED & FUTURE MARKETS

Apart from targeted cancer chemotherapy, nanotechnology is being used more widely in
creating a new generation of drug delivery systems. A key factor in its adoption is that
nanoscale particles have a greater surface-to-volume ratio than macroparticles. Thus, a drug-
bearing nanoparticle can release a drug more quickly and more abundantly than larger
particles. This is helpful when the drug poses problems with solubility and absorption, as is
the case with a considerable proportion of new drugs.

Already on the market in the US and elsewhere are wound dressings that exploit the
antimicrobial properties of nanocrystalline silver. Ionic silver is a powerful antibacterial,
effective even against problem organisms like MRSA, and nanotechnology offers a way to
optimize its effect when incorporated in a wound dressing.
While current medical nanotech applications focus on single nanoparticles and simple
structures, future possibilities will involve combing such single elements into structures that
can carry out more complex tasks than, for example, releasing drug payloads. Thus,
nanostructures may be developed that can insert probes into elected cells and inject DNA or
protein to correct genetic abnormalities.

Another possibility is to design nanostructures that can foster and direct the regeneration of
nerve cells; these would be used in the treatment of stroke and trauma victims, and possibly
for the restoration of lost function in Alzheimer’s disease. However, a sober estimate of
timing would warn us not to expect these developments to become reality until 10 to 20 years
from now.

The nanomedicine market is in early growth. While nano-enhanced drug delivery products
are already a commercial reality, more advanced nanotech-based medical devices are still in
development, although some are at the clinical testing stage.

Most of the money being spent on the wider field of nanotechnology R&D comes from
government and established corporations. In the nanomedicine field, pharmaceutical and
specialist companies are at the forefront of research into the medical applications of
nanotechnology.

To date, drug delivery has been the main near-term opportunity for medical nanotechnology.
This market has an estimated value of $15.8 billion for 2014 and is forecast to grow to $44.5
billion by 2019, to register a significant CAGR of 23%.

Advances in nanoscale science and bionanoengineering are revolutionizing our understanding

and ability to manipulate complex biological processes as well as the way health care is
administered. These approaches and innovations, collectively termed nanomedicine, are on the
verge of improving disease prevention, detection, treatment, and management. First generation
liposomal-based nanopharmaceuticals for cancer treatment reached the global market years ago
with outstanding therapeutic efficacies in many cases. Today, creative nanotechnology and
nanoscience approaches to formulation design are further improving the cause, and
secondgeneration cancer nanomedicines are beginning to prove their value. Collectively, these
nanopharmaceuticals have considerably reduced adverse drug and solvent effects as well as
being passively targeted;they take advantage of the enhanced permeability and retention effect
and other tumorvasculature-specific properties to accumulate at the sites of solid tumors.
Foreseeable progress in nanoparticle targeting of pathological sites is further expected since
emerging classes of targeting and cell-specific ligands are currently at various stages of clinical
development. These emerging classes of ligands include smaller recombinant antibody
fragments, nanobodies, and engineered variants as well as ligands discovered through
technologies such as phage, yeast, and ribosomal display and cell systematic evolution of ligands
by exponential enrichment. These ligands not only show great promise for therapeutic and
diagnostic interventions in their own right, but their small size, impressive affinity and target
specificity make them ideal candidates for conjugation to nanoparticles. Possible synergistic
effects between nanoparticle characteristics (size and geometry) and molecular targeting may
dramatically enhance specificity of delivery, thus opening the path to new and sophisticated
design solutions for clinical use. Economically, the complexity and the know-how of nano-based
approaches to formulation design have the advantage of offering market exclusivity to the
pharmaceutical industry and confronting generic threat better. Indeed, such technological
approaches are expected to deliver a reduction in and/or prevent rapid revenue falloff for
proprietary nanopharmaceuticals even after patent expiration.4 In parallel, the growing interest
in biotechnology has already begun to transition the pharmaceutical industry to biologics
research and development. Today, biopharmaceuticals account for 25% of all pharmaceuticals in
the development pipeline. An aging population and the associated increase in chronic diseases
provide significant opportunities for biologic manufacturers, where the global market is
projected to reach US$185 billion by 2015. Integrated scientific, commercial, and societal
aspects are addressed, and provocative combined realistic biotech, computational, and
nanotech approaches for tailor-made engineering of nanopharmaceuticals are discussed.
Cancer, cardiovascular diseases, diabetes, central nervous system disorders, chronic
inflammatory conditions, allergies, autoimmune diseases, metabolic disorders, and
hormone/enzyme replacement therapies are among the major therapeutic areas that are likely
to see significant biotech product launches in the next years. Increased regulatory approval rates
for biotech products compared with small molecule drug candidates are also driving growth of
the market and interest among the pharmaceutical industry. The demand for biotech products is
greatest in complex areas where conventional pharmaceutical products have been less
successful, such as in the case of multiple sclerosis. It is perceivable that future developments in
biopharmaceuticals will increasingly be driven by advances in enabling technologies such as
genomics, proteomics, pharmacogenomics, and toxicogenomics. Far greater emphasis, however,
should be placed on personalized macromolecular medicines to improve human health at all
levels.

Through such interventions, we envisage rapid developments in cancer vaccines, vaccines for
autoimmune diseases, and tailor-made treatments for cancer-based personal genomes.
Pertinent to realizing these goals, with the ultimate aim of optimizing individualized and
population-based therapies, is a need for libraries of safe and multifunctional nanomaterials and
nanoparticles that not only afford protection to biologics against the hostile in vivo
microenvironments but further achieve controlled targeted delivery and cargo release . Here, a
detailed understanding of dynamic behavior and interactive forces between macromolecular
cargo and the nanomaterial components is still required and remains central for optimization
strategies (e.g., in terms of stability optimization and developing new extra- and intracellular
release mechanisms). An integrated approach is also necessary, including not only a detailed
mapping of “structureactivity” relationships but also concomitant extensive computational
network knowledge of genomics and epigenomics of inter-individual variations to biologics
responses, thus pushing the boundary of the envisaged personalized nanomedicine therapies to
reality

High Risks, High Gains.

Today, substantial developments are arising from nanomaterial structureactivity approaches

that could dramatically reshape the future of nanopharmaceuticals and pave the way for
individualized nanomedicine therapies. Clinical evaluations are currently underway with these
formulations. Unforeseen toxicity toward manmade nanomaterials that are intended to
optimize biologics performance still remains a concern. Immunological reactions to
nanoengineered materials are particularly notable. These may comprise induction of antibody
formation against select components and pro-inflammatory reactions (via immune cell receptor
activation and signaling), particularly through repetitive epitope presentation, chemical
modification procedures, pharmacokinetic profiles, lymphocyte activation, idiosyncratic non-IgE-
mediated acute anaphylactic reactions, and intrinsic immune-stimulating properties (e.g.,
interferon response and adjuvant effects). For instance, idiosyncratic and acute anaphylactic
reactions to conventional as well as PEGylated liposomes, micellar drug formulations, and a
plethora of contrast agents have been well-documented and occur in certain individuals, while
their molecular basis is largely neglected. The incidence of acute, allergic-like responses in
pharmaceutical formulations and nanomedicines corresponds to approximately 80% of all
immunemediated hypersensitivity reactions Today, biopharmaceuticals account for 25% of all
pharmaceuticals in the development pipeline. Such outcomes impose further health and
financial burdens and may complicate the development phase of new nanomedicine initiatives.
Computation-based immunogenomic knowledge, however, could salvage this and help
immensely toward a mechanistic approach. It remains essential to unravel the molecular basis of
serious adverse immune responses at both humoral and cellular levels through structure activity
approaches. If this can be put within the framework of population genetics, then it will
ultimately provide significant gains for human health and treatment selection. Integration of
research in nanomaterial design and nanoparticle pharmacology remains a grand challenge for
controlled delivery and release of therapeutic payloads and for the molecular basis of
nanomedicine toxicity at an earlier stage and through population-based design (both at cellular
and immune system level).28 This, however, requires multicollaborative, interdisciplinary, and
innovative nanoscience, omics and other approaches to nanopharmaceutical formulation, but
will advance broad societal goals, from improved understanding of the material behavior at
molecular and individualized levels to increased productivity through nanotechnology tool
optimization, rational design, and responsible nanobased manufacturing. Ultimately, this will
expand the market for many macromolecular therapeutic agents and small molecules and will
form the basis for a highly profitable niche for biotechnology and pharmaceutical industries and,
most importantly, for human health at all levels (Table 1). In addition, generation of biologically
and environmentally safe nanoparticulate drugdelivery systems makes it possible to formulate
drugs in an optimal way and for personalized therapies; this could have a significant impact on
sustainability by helping to salvage a broad library of discarded compounds. The safe use of
nanoparticulate delivery systems and emerging personalized nanopharmaceuticals will also
create significant savings in pharmaceutical spending, which continues to grow. Any reduction in
spending on pharmaceuticals would allow funds to be spent on other treatments or on other
healthcare facilities.

It was predicated over a decade back that “nanopharmaceuticals will help prolonged life,
improve its quality, and extend human physical capabilities” and by year 2015, half of all
pharmaceutical productions, over $180 billion per year would be based on nanotechnology. At
present, nanoscale formulations and design of pharmaceutical dosage forms have become
prerequisite to sustain the growth of the pharmaceutical industry. The market for
nanopharmaceutical has made a rapid stair from $406 million in 2004 to $3 billion in 2009 and
$16.6 billion in 2015. According to a new report published by visiongain forecasts the world
market for nanopharmaceuticals will reach $130 billion in 2017.There is an active research and
increasing demand of nanopharmaceutical applications resulting in better positions in the
pharmaceutical and other health care industries [38, 39]. Conclusion The review of literature and
research of nanopharmaceuticals reveal that nanoparticulate systems have great potentials,
being able to convert poorly soluble, poorly absorbed and labile biologically active substance
into promising deliverable drugs. However, to optimize this nanopharmaceuticals delivery
system, greater understanding of the different mechanisms of biological interactions, and
particle engineering and characterization, is still essential. Further advances are needed in order
to turn the concept of nanoparticle technology into a realistic practical application as the next
generation of drug delivery system. In future, nanopharmaceuticals will greatly influence
medical practice and healthcare because of their ability, in many cases, to shorten the time-
market for active agents, extend the economic life of proprietary drugs and create additional
revenue streams. The challenge of nanotechnology is to develop nanoparticles for biomedical
and biotechnology applications, to deliver the pharmaceutical in the right place at the right time.
Some formidable challenges include legal, environmental, safety, ethical and regulatory
questions as well as emerging thickets of overlapping patent claims. Though there are few
nanopharmaceuticals in the market that have been approved by the FDA, these formulations
have immense impact in the field of therapy management and also hold greater promise in
pharmaceutical drug design and delivery.

Conclusions Nanomedicine is a promising sub-segment in medicine that took off in the 1980s
with the first generation of developed nanopharmaceuticals. With the use of nanotechnology,
drugs can be delivered in ways not experienced so far. U.S. is a strong actor in this field with
many patents having commercialized several nanopharmaceuticals. The global nanomedicine
market was valued at US$50.1 billion in 2011 and is projected to grow to US$96.9 billion in 2016.
The share of nanomedicine to the total global pharmaceutical market is estimated at 5.3 percent
in 2011 indicating its niche character presently. In Japan, for various reasons, the nanomedicine
market size in terms of the total market is much smaller. A rough estimate shows that the share
is between 1 to 2 percent corresponding to approximately US$1 to 2 billion. A limited number of
approved Japanese nanodrugs together with a long time until approved foreign products
entered the Japanese market have seemingly slowed the market expansion. Totally, sixteen
drugs have the status as nanopharmaceuticals in Japan (sub-micron size). Five of these are
manufactured by Japanese companies and developed in the 1980s and early 1990s. Currently,
there are three Japanese nanodrug candidates in clinical trials. They are all related to the
University of Tokyo and top-level research by Prof. Kataoka and his team. Three start-up bio-
ventures have been identified including NanoCarrier that has in-licensed patents owned by the
University of Tokyo. The adopted business model focuses on seeking existing drugs that are
potent but lacking carriers for effective drug delivery. The three drug candidates have attracted
international attention and some of these should have a fair chance of getting marketing
approval in the short term which could give a boost to Japan’s nanomedicine industry. In
addition to the University of Tokyo, research related to nanomedicine is conducted at Hokkaido
University, Tohoku University, Osaka University as well as research institutes such as National
Institute for Materials Science. The Japanese government has implemented various basic plans.
Initially, nanotechnology was prioritized but under the latest plan, the 4th Science & Technology
Basic Plan (FY2011-FY2015), Life Innovation has been prioritized together with Green Innovation.
With the aim of promoting the development of innovative medicine, the government is aiming
at transforming the way research is carried out. “Exit-oriented” R&D, i.e. issue-driven innovation
beyond discipline-oriented innovation, will help in speeding up innovations. Improvements in
processing drug approval applications have reduced the drug lag. Other initiatives include
cooperation with the European Medicines Agency targeting block copolymer micelles, and
enhanced functionalities of the Pharmaceuticals and Medical Devices Agency. When it comes to
opportunities for European companies, the potential is changing for the better. The improved
nanomedicine infrastructure such as clarified approval standards and shorter approval times are
some factors that will simplify and shorten the time needed for a market launch in Japan.
www.EUbusinessinJapan.eu EU-Japan Centre for Industrial Cooperation 31 Opportunities include
increased out-licensing of nanodrugs to Japanese pharmaceutical companies or the
establishment of own company for a direct launch. Alternatively, if it already has a subsidiary in
Japan let the local company launch the drug. Deregulation has made it easier to start
pharmaceutical operations in Japan. The government emphasizes the importance of increasing
joint or contracted research with overseas universities and businesses. This could create
opportunities for European universities to collaborate with Japanese universities as well as
chances for European pharmaceutical companies. As more nanodrugs enter the market in Japan
including approval of Japanese-developed products, the use of nano-scale medicine will increase
and expand the market. The need to cut healthcare expenditure in Japan will also drive the
development of innovative medicine that will give further momentum to the nanomedicine
segment.

Bridging Future Nanomedicines to Commercialization A lot of nanotherapeutics have already

gained market access worldwide. Although for nanopharmacy to show its full potential in
healthcare industry, a number of challenges remain to be addressed: Stabilization of
nanotherapeutics remains challenging. Further understanding on the principles governing
physical stability of these colloidal drugs and prevention of specific degradation routes, for
example, by formulation, remains to be elucidated. The scale-up and manufacturing of
nanotherapeutics remains variable. Process control is challenging and concerns related to the
unpredictable impact of small variations to chemistry, manufacturing, and control (CMC) on the
in vivo faith of the nanodrugs require tight controls of physicochemical properties of individual
drug batches. Well-defined analytical tools that allow the full characterization of the
nanoparticles’ safety, efficacy, and quality need further development. Existing in vitro
techniques have limitations in a way that in vitro in vivo correlation (IVIVC) cannot be performed
easily and extensive bioequivalence testing is still needed. It would be great if novel in vitro
methods become available that are straightforward to use and are predictive of the in vivo
behavior. The interested reader can learn more about developments in this field in Chapter 12
“Scale-Up and cGMP Manufacturing of Nanodrug Delivery Systems for Clinical Investigations,”
Chapter 17 “Nanoparticle Toxicity: General Overview and Insights Into Immunological
Compatibility,” and Chapter 15 “Computational Predictive Models for Nanomedicine.” Toxicity
related to nanotherapeutics remains to be further unraveled. Nanoparticles are developed in
many cases to reduce toxicity of the drug by enhanced targeting or shielding from healthy tissue.
New materials such as dendrimers may be employed as carriers. Although knowledge about the
potential toxicity of these, more recent nanocarriers themselves remain to be elucidated as well
as the potential new toxicities that may develop because of the small size of the dosage form.
Existing toxicological assessment is developed for conventional dosage forms; appropriate tests
to fully understand the toxicity of nanoparticles need further development [53]. Therefore,
regulatory hurdles to establish long-term safety of nanotherapeutics remain high with the need
for accountability for biodistribution, mass balance, long-term residence, and ultimate
elimination. The interested reader can learn more about this topic in Chapter 17 “Nanoparticle
Toxicity: General Overview and Insights Into Immunological Compatibility” and Chapter 18 “An
Overview of Nanoparticle BioBiocompatibility for Their Use in Nanomedicine.” Sophisticated
methods for the detection and more exact quantitation and biocompatibility of the
nanoparticles in tissues need further development and validation to assess short- and long-term
potential toxicities. In order to bridge these knowledge gaps, long-term collaborations between
industry and universities are very important. Such collaborations allow the 10 1 History:
Potential, Challenges, and Future Development in Nanopharmaceutical Research and Industry
scientific experts at universities to unravel the knowledge gaps that restrain industry in their
ability to develop robust nanopharmaceuticals with predictable physicochemical and biological
properties that ensure its quality, safety, and efficacy that are required to gain regulatory
approval. Governmental policies providing a predictable and stable environment of funding and
regulations nourishing such long-term partnerships have shown to be crucial for the success of
these interactions. Indeed, successful collaborations are built around a common vision, strong
professional relationships and trust, and shared benefits that allow bridging the cultural
differences between the academic and industrial world [54]. It will also contribute to the
translation of great innovative ideas with a lot of promise for the society to robust products that
can be commercialized. Indeed, currently a great culture of promise exists around
nanopharmacy in academia and small start-ups but they face a lot of challenges to manufacture
first batches of innovative nanotherapeutics according to good manufacturing practices that can
be evaluated in clinical trials and translated into commercial products beneficial for the society.
A close interaction between different stakeholders, such as researchers, patient groups,
healthcare providers, regulators, and society, will also help in advancing the impact of
nanotherapeutics on global public health. Current studies suggest that there is skepticism about
the safety of nanotechnology and its impact to the environment, while others see great
potential for the treatment and prevention of diseases such as cancer [55]. More research
driven by innovators across different disciplines is needed to continuously address knowledge
gaps regarding potential health and safety implications of nanopharmaceuticals in a way more
information becomes available regarding its impact on health outcomes and overall health care
cost. The interested reader is referred to Chapter 21 “Social Studies of Nanopharmacy” to read
more on this topic. A better understanding of the physicochemical and biological parameters
affecting the quality, safety, and efficacy of the nanopharmaceuticals will also enable “follow-
on” nanotherapeutics to gain easier access to the market. Currently, nanotherapeutic product
applications are assessed under conventional regulatory framework and it is extremely
challenging to develop nanosimilars that could be approved after the innovator patents
expiration. Therefore, the regulatory authorities have established an ad hoc expert group that
gives guidance and drafted a number of reflection papers that give scientific and regulatory
guidance for the development of follow-on nanotherapeutics and emerging next-generation
nanotherapeutics [56]. In addition, innovators developing nanotherapeutics are encouraged to
seek regulatory agency’s advice on the appropriate tests and studies to be performed during the
development of a novel nanotherapeutic. The interested reader can read more in Chapter 20
“Regulatory Issues in Nanomedicines.” 1.5 Future Outlook The use of nanotechnology in the
pharmaceutical industry has already shown great potential in increasing bioavailability, reducing
toxicity, and side effects of 1.5 Future Outlook 11 existing drugs and in improving overall health,
adherence, and comfort of patients. The technology is set to spread rapidly. Many more new
 nanotherapeutics using GRAS (Generally Recognized as Safe) or new materials are currently in
various stages of development going from early discovery to late-stage clinical trials. Although
nanotherapeutics are usually administered intravenously, recent clinical studies have also shown
great potential if dosed subcutaneously, dermally, or as aerosols [13,57]. While in the past
nanotherapies were mainly used as vaccine or cancer therapy, current advancements
encompass all major disease areas, such as Alzheimer’s disease, rheumatoid arthritis, diabetes,
gene therapy, infectious diseases, and many others. The future technologies exploit further cell-
specific targeting enabled by advancements made in the understanding of how the molecular
buildup of diseased organs differentiate from healthy tissue and how nanotherapeutics interact
in the body. In addition, developments in manufacturing technologies will enable more efficient
loading of drugs in the nanoparticles and even enable loading of two or more therapeutic agents
into one nanocarrier as, for example, in nanoparticles prepared by the layer-bylayer technology
[58]. Although the biggest leap forward in patient care that is trending more and more toward
personalized medicine, and the detection, diagnosis, and prevention of diseases can be expected
by the combination of nanotherapeutics with other nanotechnologies, including nanobots, cell
therapy, nanodevices, sensory feedback, enhanced imaging, and others. Such combinations will
undoubtedly revolutionize medical care and provide enormous benefit to the patient and society
in the management of health, disease, and potentially aging. However, strong research efforts in
an intensive cooperation of industry and universities are required to develop such
revolutionizing combinations.

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