Re: [GRG] nanoparticle pills to replace injections, method – MIT

http://www.eurekalert.org/pub_releases/2013-11/miot-pot112613.php

Contact: Sarah McDonnell
s_mcd@mit.edu
617-253-8923
Massachusetts Institute of Technology

Pills of the future: Nanoparticles

CAMBRIDGE, MA — Drugs delivered by nanoparticles hold promise for
targeted treatment of many diseases, including cancer. However, the
particles have to be injected into patients, which has limited
their usefulness so far.

Now, researchers from MIT and Brigham and Women’s Hospital (BWH)
have developed a new type of nanoparticle that can be delivered
orally and absorbed through the digestive tract, allowing patients
to simply take a pill instead of receiving injections.

In a paper appearing in the Nov. 27 online edition of Science
Translational Medicine, the researchers used the particles to
demonstrate oral delivery of insulin in mice, but they say the
particles could be used to carry any kind of drug that can be
encapsulated in a nanoparticle. The new nanoparticles are coated
with antibodies that act as a key to unlock receptors found on the
surfaces of cells that line the intestine, allowing the
nanoparticles to break through the intestinal walls and enter the
bloodstream.

This type of drug delivery could be especially useful in developing
new treatments for conditions such as high cholesterol or
arthritis. Patients with those diseases would be much more likely
to take pills regularly than to make frequent visits to a doctor’s
office to receive nanoparticle injections, say the researchers.

“If you were a patient and you had a choice, there’s just no
question: Patients would always prefer drugs they can take orally,”
says Robert Langer, the David H. Koch Institute Professor at MIT, a
member of MIT’s Koch Institute for Integrative Cancer Research, and
an author of the Science Translational Medicine paper.

Lead authors of the paper are former MIT grad student Eric Pridgen
and former BWH postdoc Frank Alexis, and the senior author is Omid
Farokhzad, director of the Laboratory of Nanomedicine and
Biomaterials at BWH. Other authors are Timothy Kuo, a
gastroenterologist at BWH; Etgar Levy-Nissenbaum, a former BWH
postdoc; Rohit Karnik, an MIT associate professor of mechanical
engineering; and Richard Blumberg, co-director of BWH’s Biomedical
Research Institute.

No more injections

Several types of nanoparticles carrying chemotherapy drugs or short
interfering RNA, which can turn off selected genes, are now in
clinical trials to treat cancer and other diseases. These particles
exploit the fact that tumors and other diseased tissues are
surrounded by leaky blood vessels. After the particles are
intravenously injected into patients, they seep through those leaky
vessels and release their payload at the tumor site.

For nanoparticles to be taken orally, they need to be able to get
through the intestinal lining, which is made of a layer of
epithelial cells that join together to form impenetrable barriers
called tight junctions.

“The key challenge is how to make a nanoparticle get through this
barrier of cells. Whenever cells want to form a barrier, they make
these attachments from cell to cell, analogous to a brick wall
where the bricks are the cells and the mortar is the attachments,
and nothing can penetrate that wall,” Farokhzad says.

Researchers have previously tried to break through this wall by
temporarily disrupting the tight junctions, allowing drugs through.
However, this approach can have unwanted side effects because when
the barriers are broken, harmful bacteria can also get through.

To build nanoparticles that can selectively break through the
barrier, the researchers took advantage of previous work that
revealed how babies absorb antibodies from their mothers’ milk,
boosting their own immune defenses. Those antibodies grab onto a
cell surface receptor called the FcRN, granting them access through
the cells of the intestinal lining into adjacent blood vessels.

The researchers coated their nanoparticles with Fc proteins — the
part of the antibody that binds to the FcRN receptor, which is also
found in adult intestinal cells. The nanoparticles, made of a
biocompatible polymer called PLA-PEG, can carry a large drug
payload, such as insulin, in their core.

After the particles are ingested, the Fc proteins grab on to the
FcRN in the intestinal lining and gain entry, bringing the entire
nanoparticle along with them.

“It illustrates a very general concept where we can use these
receptors to traffic nanoparticles that could contain pretty much
anything. Any molecule that has difficulty crossing the barrier
could be loaded in the nanoparticle and trafficked across,” Karnik
says.

Breaking through barriers

In this study, the researchers demonstrated oral delivery of
insulin in mice. Nanoparticles coated with Fc proteins reached the
bloodstream 11-fold more efficiently than equivalent nanoparticles
without the coating. Furthermore, the amount of insulin delivered
was large enough to lower the mice’s blood sugar levels.

The researchers now hope to apply the same principles to designing
nanoparticles that can cross other barriers, such as the blood-
brain barrier, which prevents many drugs from reaching the brain.

“If you can penetrate the mucosa in the intestine, maybe next you
can penetrate the mucosa in the lungs, maybe the blood-brain
barrier, maybe the placental barrier,” Farokhzad says.

They are also working on optimizing drug release from the
nanoparticles in preparation for further animal tests, either with
insulin or other drugs.

###

The research was funded by a Koch-Prostate Cancer Foundation Award
in Nanotherapeutics; the National Cancer Institute Center of Cancer
Nanotechnology Excellence at MIT-Harvard; a National Heart, Lung,
and Blood Institute Program of Excellence in Nanotechnology Award;
and the National Institute of Biomedical Imaging and Bioengineering.

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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