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Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston. His research group is
working on various nanotechnologies. We had an opportunity to discuss some aspects of nanotechnology
and its applications
research interest.
We are working on three different types of nanoplatforms: polymeric, lipid-based, and metal-based. In
polymeric nanosystems, we are interested in using hydrophilic and hydrophobic biodegradable and
biocompatible polymers for drug and gene delivery, respectively. We have developed long-circulating poly
(epsilon-caprolactone) nanoparticles for delivery of paclitaxel and tamoxifen to tumors. In collaboration
with Professor Robert Langer’s group at MIT, we are exploring the use poly(beta-amino ester)
nanoparticles for pH-responsive drug delivery to hypoxic tissues such as tumors and inflammatory areas.
Recent studies in our lab are focused on multifunctional polymeric nanoparticles that can deliver more than
one therapeutic agent and over drug resistance in cancer.
For gene delivery, our focus has been to use gelatin based nanoparticles for systemically-administered
tumor gene therapy. We have carried extensive studies with reported plasmids encoding for GFP or beta-
galactosidase. Recently, we have used long-circulating thiolated gelatin nanoparticles for sFlt-1 (VEGF
receptor-1) plasmid DNA for anti-angiogenic gene therapy in breast cancer. We are working on other gene
therapy strategies using gelatin-based nanocarriers for cancer and inflammatory diseases.
On the lipid nanoparticles, we have developed oil-in-water nanoemulsions, were the oil droplets are reduced
to less than 100 nm in diameter. Using oils rich in omega-3 polyunsaturated fatty acids (PUFA), we find
very interesting biological properties, such as enhanced absorption through the gastrointestinal tract and
transport across the blood-brain barrier. These nanoemulsions are extremely versatile in terms of choices of
oils, the types of surfactants, and the payload that can be encapsulated and delivered to specific sites in the
body. We have also included gadolinium ions in the nanoemulsions to provide contrast enhancement in MRI
for image-guided cancer therapy.
Our metal nanoparticles are primarily based on gold, silver, and iron chemistry. We have prepared variety of
gold nanoparticles (spheres, rods, etc) with different optical properties. Silver nanoparticles find interesting
antimicrobial activity and we have developed silver nanoparticles-polymer complexes as materials with
intrinsic antimicrobial properties. Iron oxide nanoparticles are commonly for contrast enhancement in MRI.
We are also interested in using iron oxide nanoparticles for A/C magnetic hyperthermia. Using iron oxide-
poly(epsilon-caprolactone) nanocomposites, we can design heat-triggered drug delivery system for
hyperthermia and ablation.
What do you think are the bottle necks for targeting drugs to tumor tissue using polymeric/metal
nanoparticles?
I believe safety of the material will be the key issue/bottle neck. We are starting to see nanosystems of
different kinds being used, especially for cancer imaging and therapy. Unfortunately, for many of these
nanosystems, attention is primarily focused on how to get them to the tumor and what functionality they
will provide. Most investigators do not concern themselves with what will happen to the nanosystems once
it accomplishes its function. How will it be cleared from the body? Appropriate pharmacokinetic
considerations need to be included in nanosystems design and in vivo testing is going to be absolutely
critical, if we envision any kind of success.
There is also growing interest in developing nano-carriers for gene delivery, which seems to be
more complex than drug delivery, what is the present scenario in this area of research.
I have very interesting perspective in non-viral gene delivery systems. I edited a book “Polymeric Gene
Delivery: Principles and Applications”, which was published by CRC Press in 2004. Our effort in gene
delivery started after I completed my sabbatical appointment in Professor Langer’s lab at MIT in 2000.
When I saw that the mail limitation was endosomal/lysosomal release, I realized that cationic lipids and
polymers are probably not the way to go. Therefore, we started to look at type B gelatin-based
nanoparticulate gene delivery system, where the pH of formulation is intentionally kept at 7.0 in order to
have a net negative charge on the protein. Instead of electrostatic interactions, this system allows for
physical encapsulation of the plasmid and, more importantly, retains the supercoiled structure of the
plasmid. In my opinion the supercoiled DNA structure is critical for nuclear import of the plasmid in non-
dividing cells. We have made PEG-modified gelatin nanoparticles for long circulation and passive tumor
targeting. Recently, we have developed thiolated gelatin and PEG-modified thiolated gelatin nanoparticles
that release the payload in response to reducing environment present in solid tumor and inflammatory areas.
The PEG-modified gelatin and thiolated gelatin nanoparticles have already shows very impressive
transfection potential of sFlt-1 plasmid DNA in human breast cancer xenograft model.
Polymers are being used as carriers for delivery of drugs, most of them are meant to release their
payload of drug out side the cell. However nano-carriers are studied extensively for delivery of drug
either into the cell or to the nucleus, what are the possible toxicological issues when theses carriers
are used for long term therapy.
A lot of toxicological implications will be dictated by the type of polymeric or other nanocarrier systems
that are used. If one chooses to use biocompatible materials and develop them in nanoparticulate
formulations (as we intentionally have), then the risk of toxicity in the cell or sub-cellular organelle is fairly
low. However, if one chooses to work with silica or carbon-based nanosystems, where the toxicological
issues are not well addressed, then it is highly possible that there will be consequences in the short-term and
the long-term.
Researchers across the world are working on various area of drug targeting using polymeric
nanoparticles, what are the hurdles in putting a nanoparticle based product in the market.
Much of the work in polymeric nanoparticles for drug delivery utilizes “off the shelf” materials. In some
cases, this is okay since you are able to find the desired physical, chemical, and biological properties in
these systems. However, as demand for more sophisticated materials grows, it will be important to
synthesize polymeric materials in high throughput fashion. Some laboratories, such as Professor Langer’s,
have already done an excellent job with this idea. Poly(beta-amino esters) are a class of biomaterials
synthesized by high throughput and tested for biocompatibility and DNA transfection potential. Currently,
more than 5,000 different types of poly(beta-amino esters) are available. Therefore, it is clear that material
development will be a key to success.
The other side for targeted drug delivery systems is greater and discriminatory understanding of the disease
target. We have to insure that the targets are sufficiently robust and only expressed at the disease sites to be
able to provide the specificity that are needed.
Last aspect of polymeric nanoparticles for drug delivery is multifunctionalization either by inclusion of more
than one therapeutic agent (e.g., antiangiogenic and cytotoxic drug combination), multidrug resistance
modulator and therapeutic agent, imaging and therapeutic agent combination, etc.
As the systems get more complicated, quality control issues will become highly complex. The National
Cancer Institute’s Alliance for Nanotechnology in Cancer (http://nano.cancer.gov) has setup the
Nanotechnology Characterization Laboratory (NCL) for providing complete preclinical characterization of
nanosystems intended for cancer prevention, diagnosis, and therapy. NCL works with the National Institute
of Standards and Technology (NIST) and the Food and Drug Administration (FDA) to develop appropriate
standards for quality control as well as in vitro and in vivo preclinical testing methodologies for safety and
efficacy evaluations. At the end, FDA has and will continue to approve nanotechnology products that are
deemed to safe and efficacious.
Research in the area of Nanomedicine requires pharmaceutical scientist to acquire an additional
knowledge base, like material science, molecular biology, surface chemistry etc. How best
curriculum or research training in the pharmacy schools is matching these requirements?
Many agencies, such as the National Institutes of Health (NIH) and the National Science Foundation (NSF)
in the U.S., are recognizing the need for interdisciplinary graduate education model. This model focuses
more on problem solving rather discipline-specific training. For instance, we have received a $3.3 million
NIH/NSF training grant in Nanomedicine Science and Technology through their Interdisciplinary Graduate
Education and Research Training (IGERT) program. This grant will support up to 10 doctoral fellows per
year who choose Nanomedicine training provided by interdisciplinary faculty from Pharmaceutical
Sciences, Chemistry, Biology, Physics, Chemical Engineering, and Mechanical Engineering. Both didactic
courses as well The program also involves mandatory internship requirement in industry, academic
research lab, or medical research lab. We already have 6 IGERT fellows in the program working on
different aspects of Nanomedicine. For details of this program, visit http://www.igert.neu.edu.
Pharmaceutical Sciences curriculum and research training will also need to be adapted to fit the needs of
graduates in the future. In many instances, universities are not good at revolutionary changes. However, as
demand for graduates who have nanomedicine training increases, the market forces will drive universities to
modify their curriculum and research training.
There is lot of hype both in academia and industry about nanotechnology based products, do you
think nanotechnology will meet the expectations
Hype is nothing new when a new idea is put forth. The pragmatist in the field can filter through the hype
and see what are going to be the real benefits. I personally believe that nanotechnology will have a very role
to play in prevention, diagnosis, and therapy of various diseases.
Some of the publications of Prof. Amiji`s group
Books
Amiji, M.M. (Ed.) Polymeric Gene Delivery: Principles and Applications. CRC Press, LLC (a subsidiary of
Taylor and Francis). Boca Raton, FL. 2004.
Amiji, M.M. (Ed.). Nanotechnology for Cancer Therapy. CRC Press, LLC (a subsidiary of Taylor and
Francis). Boca Raton, FL. (In press).
Peer-reviewed manuscripts:
Kabul, G. And Amiji, M. Tumor-targeted delivery of plasmid DNA using poly(ethylene glycol)-modified
gelatin nanoparticles: In vitro And in vivo studies. Pharmaceutical Research 22(6): 951-961 (2005).
Shenoy, D., Little, S., Langer, R., And Amiji, M. Poly(ethylene oxide)-modified poly(beta-amino ester)
nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: Part I. In vitro
evaluations. Molecular Pharmaceutics, 2(5): 357 -366 (2005).
Shenoy, D., Little, S., Langer, R., And Amiji, M. Poly(ethylene oxide)-modified poly(beta-amino ester)
nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: Part II. In vivo
biodistribution And tumor localization studies. Pharmaceutical Research 22(12): 2107-2114 (2005).
Kommareddy, S., Tiwari, S., And Amiji, M.M. Long-circulating nanovectors for tumor-specific gene
delivery. Technology in Cancer Research And Treatment. 4(6): 615-626 (2005). (Special issue on
Nanotechnology in Cancer Detection And Treatment).
Shenoy, D., Fu, W., Li, J., Crasto, C., Jones, G., Dimarzio, C., Sridhar, S., And Amiji, M. Surface
functionalization of gold nanoparticles using hetero-bifunctional poly(ethylene glycol) spacer for intracellular
tracking And delivery. International Journal of Nanomedicine 1(1): 51-57 (2006)
van Vlerken, L.E. And Amiji, M.M. Multifunctional polymeric nanoparticles for tumor-targeted drug
delivery. Expert Opinion on Drug Delivery 3(2): 205-216 (2006).
Tiwari, S.B., Shenoy, D.B., And Amiji, M.M. A review of nanocarrier-based CNS delivery systems.
Current Drug Delivery 3: 219-232 (2006).
Patents
Amiji, M.M. “Biocompatible Articles And Method of Making Same”. United States Patent Number
5,885,609. Issued: March 1999.
Amiji, M.M. “Drug Delivery Using pH-Sensitive Semi-Interpenetrating Network Hydrogels”. United States
Patent Number 5,904,927. Issued: May 1999.
Langer, R.S., Lynn, D.M., Putnam, D., Amiji, M.M., And Anderson, D.G. “Biodegradable Poly(Beta-Amino
Esters) And Uses Thereof”. United States Patent Number 6,998,115. Issued: February, 2006.
Research Group Photo
For more information contact
Mansoor M. Amiji, RPh, PhD
Associate Professor And Associate Department Chair
Department of Pharmaceutical Sciences
School of Pharmacy
Co-Director, Nanomedicine Education And Research Consortium (NERC)
Northeastern University
110 Mugar Life Sciences Building
Boston, MA 02115
Email: m.amiji@neu.edu
