Re: [GRG] Nanoparticle Pills To Replace Injections (Fc Protein)

Joe: Can MIT/Harvard upstage MannKind if it can deliver
insulin orally? 
BTW, I finally did view the movie “Forks over Knives” on
The WW-II starvation of the Dutch was highly convincing that
vegetarianism is good for longevity. — Steve Coles  
At 02:28 PM 11/27/2013, you wrote: Sarah McDonnell
Massachusetts Institute of Technology
Pills of the Future:
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. 27th on-line 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
    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 11x 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 (BBB), which prevents many drugs from reaching the
    “If you can penetrate the mucosa in the
intestine, maybe next you can penetrate the mucosa in the
maybe the Blood-Brain Barrier
(BBB), 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.

About Johnny Adams

My full-time commitment is to slow and ultimately reverse biological aging and age related decline for more years of healthy living. 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 Aging Intervention Foundation (dba for Carl I. Bourhenne Medical Research Foundation), an IRS approved 501(c)(3) nonprofit. 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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