Slide 1 - Who we are

Presented by
Tamar Chachibaia, PhD candidate
• Conception of medical nanorobotics first was
described by pioneer of nanomedicine, practitioner
futurist, Robert A. Freitas Jr.
• ”Respirocytes” is the short title of the original
technical paper - “A Mechanical Artificial Red Cell:
Exploratory Design in Medical Nanotechnology”,
which was issued in 1996.
CREDIT:
URL:
Nanomedicine
Art Gallery
http://www.fore
sight.org/Nano
medicine/Galler
y/index.html
Tiny diamondoid spheres, known as respirocites, representing
hypothetical new class of medical device, filled with high pressure
oxygen could release gases at a constant rate. Mechanical rotor
maintains diffusion and exchange of oxygen, carbon dioxide, and water
around the respirocyte – providing locomotion through the body.
Blood substitutes are oxygen-carrying fluids
• In his monograph R. Freitas highlights
existing artificial respiratory gas carriers
such as hemoglobin formulations and
perfluorocarbon emulsions. These two
concepts differ significantly from each
other in several aspects.
• 1st class of oxygen-carrying fluids are
naturally occurring respiratory pigment,
haemoglobin (Hb), second is synthetic,
chemically inert, based on fluorinated
liquids called perfluorochemicals (PFCs).
Commercial products in both categories
have been developed and some approved
for clinical use, primarily to facilitate
oxygen supply to tissues during surgery or
therapy.
HOW THE RESULTS OF THE PROJECT WILL
CONTRIBUTE TO IMPROVED SECURITY?
Not only atomic bomb explosions and nuclear
powerplant accidents may raise awareness of lay
people. Stunning criminal case committed against
former Russian resident in London unleashed dreadful
disadvantage of radiation danger for citizens as
obvious threat to their security.
 In the time of asymmetric warfare, those countries
and groups with less conventional power will look for
unconventional methods. These include nuclear,
biological, and chemical weapons. Only through
research will we know the extent to which
nanotechnologies may be used in these
unconventional methods. Studies of nanotechnologies
would be directed at defence rather than offensive
tools to counteract measures of effect on people of
radiological nuclear agents and weapons.

Research is fostered by:
1. permanent shortages of donor blood supply, as well
2. risk awareness of HIV and Hepatitis viruses infections,
3. blood-type mix-up during transfusion.
Precautionary alert is raised about dissemination of
4. specific protein, termed as prion, which is responsible
for spongiform encephalopathy, capable to provoke
disastrous outbreak of human variant Creutzfield-Jacobs
disease.
Along with physiological and economic aspects, public perception
should be recognized about benefits and risks, associated with
transfusion of blood, blood products or potential blood substitutes.
Recent survey performed among young adults in UK finds that
medical and law students differ over transfusion medical ethics.
Particular clerical and cultural objection
• In the special sections of medical manuals one can find
numerous case studies with the descriptions of treatment
guidelines, proposed to save critically ill patients in
intensive care units without whole blood supply.
Synthesized blood substitutes sought to match patient’s
needs equally, while blood loss may cause inevitable threat
of life. Suggestion by doctors to their patients alternative
choice of nonblood treatment may facilitate to better
cooperation between them, lower the emotional tension and
avoid risk of religious stigma. Perhaps bloodless surgery is
only an alternative therapy for Jehovah's Witnesses, thus
bovine hemoglobin derived oxygen carriers is acceptable by
Jehovah's Witnesses as yet.
Nanotechnology perfluorocarbon
emulsions (PFCE)
• The risk of disease transmission, bacterial contamination or
blood-type mix-up is entirely excluded by using a nonbiological or ‘abiotic’ oxygen carrier, that has been on-going
for many years. First experiments with perfluorocarbon
(PFC) compounds conducted in the 1960's paved the way
for developing totally synthetic chemicals, that can dissolve
and transport oxygen and other gases. While
perfluorocarbon emulsions (PFCE) may never surpass the
practice of blood transfusion, they have potential to reduce
the need for transfused blood and to explore additional
applications, such as conservation of organs for
transplantation, in cardio-pulmonary bypass and other
blood preserving manipulations.
Nanotechnology perfluorocarbon emulsions (PFCE)
Fluosol-DA (Green Cross Corp., Japan)
&
OXYGENT (Alliance Pharmaceutical Group)
• Currently only some recognized perfluororganic carbon
emulsion (PFCE) with gas transporting function are
presented on the world market. In 1989 FDA first approved
Fluosol-DA (Green Cross Corp., Japan) for use during
angioplasty. It was withdrawn just five years later.
Company began developing a second generation PFC
called PHER-O2 in an effort to overcome the shortcomings
of Fluosol.
• Another prominent preparation OXYGENT developed by
Alliance Pharmaceutical Group - Johnson & Johnson in
2007 is applied for FDA approval.
anotechnology perfluorocarbon
emulsions (PFCE) Perftoran
Credit: G. R. Ivanitsky, 2008, July 09.
• Another PFC-based oxygen carrier, Perftoran, was
approved in 1996 for clinical use in Russia, which was
originally developed at the Institute of Theoretical and
Experimental Biophysics (Puschino, Russia), but
relatively little information is available in the English
literature for this product, hence it is not yet FDA
approved.
• More than thousands of patients participated in clinical
studies of Perftoran. The indication statement for
Perftoran claims that it is to be used in case of
hemorrhagic and traumatic shock, blood losses, multiple
trauma, burning of large surface of skin, conditions of
apparent death, ischemic brain edema and acute
ischemia, in regional perfusion to treat limb ischemia.
Why Perftoran?
Perftoran is considered to be the safest of the rest PFCEs. Average
particle size in the Perftoran emulsion is in range of 65-70 nm. This
is most optimal dimention of molecules in nanothechnology
practice, as is determined by US National Nanotechnology
Initiative guidelines. Particle size and surface characteristics are
determining factors for decrease of reactivity of preparation. While
altered erythrocytes fail to squeeze through contracted capillaries,
or lumen, sludged by aggregated blood calls, 70 nm size
molecules of Perftoran easily deliver gases to the oxygen deprived
tissues, simultaneously carry carbon dioxide from tissues and
transport it to the lungs for removal.
Perftoran particles are removed from the bloodstream within 18-24
hours after administration.
Understanding Size
• 1 nanometer
source: CERN
http://microcosm.web.cern.ch/microcosm
Capillary cross-section
with red blood cells or
erythrocytes inside.
Capillaries are the small
blood vessels that connect
arteries and veins.
Red blood cells carry
oxygen throughout the
body. SEM X5140
Credit: Photo by
Kessel and Kardon,
Visuals Unlimited
Definitions of Nanotechnology adopted by FDA
• FDA has not established its own formal definition .. FDA currently relies
on the NNI definition.
• National Nanotechnology Initiative (NNI):
– Nanotechnology is the understanding and control of matter at dimensions of
roughly 1 to 100 nanometers, where unique phenomena enable novel
applications. …. At the nanoscale, the physical, chemical, and biological
properties of materials differ in fundamental and valuable ways from the
properties of individual atoms and molecules or bulk matter.
• NCI Cancer Nanotechnology Plan (July 2004):
– Nanotechnology refers to the interactions of cellular and molecular
components and engineered materials - typically clusters of atoms,
molecules, and molecular fragments - at the most elemental level of
biology. Such nanoscale objects - typically, though not exclusively, with
dimensions smaller than 100 nanometers - can be useful by themselves or
as part of larger devices containing multiple nanoscale objects.
The image to the right is a picture taken of a mouse completely
submerged in liquid perfluorocarbon and still breathing!
• In 1966: first report of mice immersed in a
perfluorocarbon liquid saturated with oxygen;
mice survived up to 10 minutes
• На каждый эритроцит приходится свыше 105 частичек
эмульсии Перфторана. Таким образом, эффективная
поверхность 105 молекул Перфторана больше по
сравнению с суммарной поверхностью одного
эритроцита. Несмотря на то, что кислородная ёмкость
ПФ приблизительно в 5 раз ниже цельной крови,
благодаря оптимальному размеру частичек эмульсии
Перфторана т.е. 70 нм, они способны проникать в
стенозированный или закупоренный просвет
капилляров, в местах недоступных для эритроцитов
из-за их размера и деформации мембраны.
Effects of Perftoran
• Перфторан в большей степени оказывает не антианемическое действие, а точнее анти-ишемическое
на тканевом и органном уровнях вследствии
комплексного антигипоксического защитного
механизма. То что до определенного момента
является защитной функцией крови, впоследствии
может служить повреждающим тригером (пусковым
механизмом). В биологической крови присутствуют
медиаторы воспаления, цитокины, активированные
тромбогенетические факторы, фибрин и др.
• Преимущество Перфторана заключается в том, что
препарат лишен данных свойств биологической
крови и является интактным для эндотелия.
PFCE Perfluorocarbon emulsion
•
•
Перфторан может стать средством спасения для
той группы больных, которые находятся на
лечении в палатах интенсивной терапии и шанс
на улучшение общего тяжелого состояния не так
велик.
У пациентов, попавшим в палату интенсивной
терапии с тяжелыми состояниями различного
генеза в большинстве случаев, т.е. от 40 до 100%
по данным разных клиник, развивается т.н.
«Синдром эутиреоидного недуга».
Отмечается критическое падение гормонов
щитовидной железы, которое может наступить в
течении 2-3 часов.
•
Смертность высокая и достигает 85%.
Негативным прогностичским критерием является
показатель Т4 ниже 2 ug/dl. При показателях Т4
ниже 4 ug/dl погибает половина больных .
Alternative treatment
options using Perftoran
additionally to complex
intensive insulin therapy in
“Euthiroid Sick Syndrome”
and possible role on
improvement of morphfunctional status of the
kidney .
PFCE Perfluorocarbon emulsion
• Действие тиреоидных гормонов в организме на поглощение
кислорода, обмен газов, окислительные процессы хорошо
изучены, как на целом организме, так на органном и тканевом
уровнях.
• Вопрос о применении заместительная терапии по сей день
остается открытым. Использование тироксина однозначно не
даёт никаких результатов.
• Поиску новых средств, способных внести перелом в хрупком
равновесии в борьбе за жизнь пациента уделяется немало
усилий, времени и ресурсов. Препарат Перфторан может
служить тем звеном, который внесет перелом в равновесии в
борьбе за жизнь пациента, тем более что успешно применяется
в интенсивной терапии в течении последних лет.
Georgian National
NanoInnovation Initiative
is the Alliance Union inclusive of
Initiative Group &
NanoInnovation Center
http://gnni.com.ge
Founder Georgian National NanoInnovation Initiative
& CEO of NanoInnovation Center:
Ms. Tamar Chachibaia
Tel/Fax: +(99532) 454556
E-mail: [email protected]
Thank you for your time