Nanotechnology & Medicine - ianano.org Nanobio - Nanomedicine.pdf · Dendrimer/microbicide Topical microbicide for HIV FDA Fast Track (Phase II) StarPharma Definity ® Nanolipid/perflutren
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Nanobiotechnology is the branch of nanotechnology focusing on the biological and biochemical applications or uses.
The term bionanotechnology is often used interchangeably with nanobiotechnology.
Bionanotechnology normally refers to the biological or life science aspects in the design, fabrications, production and applications of nanostructures or nanodevices.
Nanomedicine is the medical application of nanotechnology.
Nanomedicine focuses on the state-of-the-art research topics such as : treatment of diseases using nanoscale formulation of drugs and biologics, targeted drug delivery systems, biosensors, nanotoxicity
In April 2006, the journal Nature Materials estimated that 130 nanotech-based drugs and delivery systems were being developed worldwide.
Paclitaxel is one of the best antineoplastic drugs found in nature.
Paclitaxel s highly hydrophobic with water solubility less than 0.03 mg/L. Its current clinical dosage from Taxol® is formulated in Cremophor EL, which has been found to be responsible for serious side effects including hypersensitivity reactions, nephrotoxicity, neurotoxicity and cardiotoxicity.
Paclitaxel
14
New formulation of Paclitaxel contained in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs)
Nanoparticles Paclitaxel can be are prepared by the solvent extraction/evaporation method with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) as a novel emulsifier.
Nanoparticles Formulation of Paclitaxel was found to be 1.37 times more effective than Taxol® after 24 hour culture at 500 ng/ml Paclitaxel concentration.
The drug loaded PLGA nanoparticles can be used either for local delivery by balloon catheter or for development of a novel type of cardiovascular stent which is coated by nanoparticle formulation instead of the pristine drug.
Photomicrograph shows paclitaxel in albumin nanoparticles seen under electron microscope at x39.000 magnification. Round albumin nanoparticles are arranged on formvar carbon—coated grid of electron microscope. Arrows indicate nanoparticles
(Damascelli, B. et al. Am. J. Roentgenol. 2003;181:253-260 )
Why prefer the nanoparticle formulation is preferred over bulk formulation?
The reason is that pure paclitaxel is not bioadhesive to the cell membrane due to its poor pharmaceutical properties, including the MDR (multiple drug resiatence) effect.
Clinical research has demonstrated that nanoparticles are more adhesive to, and thus easier to be taken than the microparticle formulation and the free drug itself.
Abraxane (paclitaxel protein-bound particles for injectable suspension), a next generation taxane, and the first in a new class of albumin-bound nanotechnology, was approved for the treatment of metastatic breast cancer.
( Ref: US Oncology)
Paclitaxel Nanoparticles
17
Self-regulated Therapeutic Agent Delivery System and Method
The patented NanoBio Drug Delivery System is based on the advanced development of the novel nanostructure bio-electric membrane for drug delivery and diagnostic applications.
Scanning electron micrograph from the Cornell Nanofabrication Facility shows rat hippocampal neurons cultured on a silicon pillar structure. Photo credit: Andrea M. P. Turner, Stephen W. P.
Turner, Natalie Dowell, Jim Turner, William Shain and Harold Craighead.
Nanoscience experiment of Neurons
Nanobiotechnology studies into the effect of surface topography on the attachment and growth of central nervous system could lead to improved devices for restoring neural function in injured patients.
• Qdots are generally composed of atoms from groups II–VI or III–V of the periodic table
• Qdots have size-tunable emission (from the ultraviolet to the infrared), narrow spectral line widths , high luminescence, continuous absorption profiles, and stability against photobleaching
Subcellular localization of QDS. PEG-QDs were conjugated to localization sequence peptides, which permit active transport to the nucleus or mitochondria. Here, fluorescence and phase contrast micrographs of a HeLa cell 24 hr after co-injection of NLS-QDs with 70kDa rhodamine dextran control.
Redrawn and adapted from Fung Biomechanics: Mechanical Properties of Living Tissue, Springer-Verlag, New York, 1993 and Keaveny and Hayes, Bone 7:285, 1993.
(Goodman S.L. et al., Biomaterials. 1996 Nov;17(21):2087-95.
Cast Replica of Vascular Tissue Demonstrating Nanometer
Roughness *
• Due to the presence of numerous nano-structures (i.e., proteins) in the body, cells are accustomed to interacting with surfaces that have a large degree of nanometer roughness.
• Despite this fact, current syntheticmaterials used as tissue engineeringscaffolds possess conventional surface features only.
Nanophase Materials
for Tissue Engineering
Ways to Synthesize Nanophase
Materials
There are many techniques to synthesize nanophase materials(or nano-structured surface roughness):
• Physical Vapor Synthesis• Electro-explosion,• Chemical Vapor Deposition (CVD),• Sol-gel, • Nanolithography, • Chemical Etching, and• etc.
Physical Vapor Synthesis was used:– Arc energy applied to solid metal which creates a vapor at high temperature.– A reactant gas is added and cooled at a controlled rate.– The vapor condenses to form nanoparticles with a defined crystalline.
Nanospherical Ceramic Synthesis
From T. J. Webster, in Advances in Biochemical Engineering/Biotechnology(K. Lee and D.L. Kaplan, editors), Springer-Verlag, in press, 2005. 35
What are the nanoparticle’s pathways inside the human body?
How long do the nanoparticles remain in the tissues and how are they cleared?
What effects do nanoparticles have on cellular and tissue functions?
Can nanoparticles gain access to the systemic circulation from dermal exposure? If nanoparticles enter skin cells, is there an effect on cellular functions?
1. Researchers in the University of Texas found that carbon nanotubes squirted into the trachea of mice caused serious inflammation of the lungs and granulomas(tumour-like nodules of bloated white blood cells in the lining of the lungs), and five of the nine mice treated with the higher dose died.
2. In a similar experiment carried out at the National Institute of Occupational Safety and Health (NIOSH) in Morgantown, West Virginia, researchers not only found granulomas in the lungs, but also damage to mitochondrial DNA in the heart and the aortic artery, and substantial oxidative damage, both foreshadowing atherosclerosis.
3. In another similar experiment in Tottori University, Japan, researchers showed that within a minute of contacting the mice’s tiniest airways, carbon nanotubes began to burrow through gaps between the surface lining cells and into the blood capillaries, where the negatively charged nanoparticles latched onto the normally positively charged red blood cells surface, thereby potentially causing the red blood cells to clump and the blood to clot.
4. Researchers from the University of Rochester, New York, reported anincreased susceptibility to clotting in rabbits that had inhaled buckyballs.
5. Buckballs present in water at 0.5 parts per million were taken up by largemouth bass, which suffered severe brain damage 48 hours later, the extent of damage being 17 times greater than that seen in controls.
6. Carbon Nanotubes in the lungs are translocated to the circulatory system and from there throughout the body, accumulating in the liver, spleen, and bone marrow. Carbon Nanotubes inhaled through the nose and air passages are translocated to the brain through the olfactory nerves, and accumulate in the brain.
7. Nanoparticles can enter the body through the skin; and quantum dots injected into the skin accumulate in lymph nodes with potential effects on the immune system [5].
8. Quantum dots consisting of a core of fluorescent cadmium selenide, touted as a non-invasive way to image internal body tissues, break down in the body, releasing cadmium, a toxic heavy metal [6].
9. Lawrence Berkeley National Lab team working with laboratory-grown cells showed that carbon nanotubes specifically activate "cell suicide genes.
What are the nanoparticle’ pathways inside the human body?
How long do the nanoparticles remain in the tissues and how are they cleared?
What effects do nanoparticles have on cellular and tissue functions?
Can nanoparticles gain access to the systemic circulation from dermal exposure? If nanoparticles enter skin cells, is there an effect on cellular functions?
Toxic Substances Control Act15 U.S.C. s/s 2601 et seq. (1976)
The Toxic Substances Control Act (TSCA) of 1976 was enacted by Congress to give EPA the ability to track the 75,000 industrial chemicals currently produced or imported into the United States.
EPA repeatedly screens these chemicals and can require reporting or testing of those that may pose an environmental or human-health hazard.
EPA can ban the manufacture and import of those chemicals that pose an unreasonable risk.
Registration Evaluation Authorization of Chemicals
New chemicals. A new chemical is defined as one that does not appear on the EINECS (European Inventory of Existing Commercial Substances) inventory. When a new chemical is produced, before introduction to the market, the producer of that chemical is required to conduct testing, and in the meantime take such precautions as are practicable. The level of testing required is determined by the mass produced, with the lowest mass trigger currently set at 10kg per annum.
Only changes in chemical structure constitute a new substance, whereas changes in form (for example size or shape) do not. An exception is made for polymers: those produced entirely from EINECS listed monomers are exempt from notification.
Mass (tonnage) triggers: Essentially, the more of an existing substance that is produced, the more data on its properties are required by regulators.
After asbestos are inhaled, they can remain and accumulate in the lungs. Asbestos can cause lung cancer, mesothelioma (a cancer of the chest and abdominal linings), and asbestosis (irreversible lung scarring that can be fatal). Symptoms of these diseases do not show up until many years after exposure began.
Argentina
Australia
Austria
Belgium
Bulgaria
Chile
Crotia
Cyprus
Czech Republic
Denmark
Egypt
Estonia
Finland
France
Gabon
Germany
Greece
Honduras
Hungary
Iceland
Ireland
Italy
Japan
Korea
Kuwait
Latvia
Lithuania
Luxembourg
Malta
Netherlands
New Zealand
New Caledonia
Norway
Poland
Portugal*
Saudi Arabia
Seychelles
Slovakia
Slovenia
Spain
Sweden
Switzerland
United Kingdom
Uruguay
South Africa
(Source: compiled by Laurie Kazan-Allen)
CURRENT ASBESTOS BANS AND RESTRICTIONS
(Revised April 2008)
The USA, Canada and Russia are 3 major developed countries that have not totally banned Asbestos
• In 1979 EPA issued a notice of its intent to regulate asbestos under the authority of Section 6 of the Toxic Substances Control Act (TSCA).
• Asbestos producers and the Canadian government began to pressure the Reagan Administration to halt EPA's efforts. Canada took a particular interest in the matter because 95 percent of the 85,000 tons of asbestos used in the US came from Canada, primarily Quebec.
• In 1989, after conducting a ten year study, EPA announced that it would phase out and ban virtually all products containing asbestos.
• EPA's stated rationale for the ban was simple: "asbestos is a human carcinogen and is one of the most
hazardous substances to which humans are exposed in both occupational and non-occupational settings."
• Proposals to ban asbestos in the United States were announced on June 18, 2002 by Senator Patty Murray
• Asbestos product manufacturers and industry organizations swiftly filed a lawsuit challenging the ban's validity under TSCA in Corrosion Proof Fittings v. EPA.
• The Fifth Circuit vacated the ban, finding that EPA failed to present "substantial evidence" to justify the ban under TSCA.
• The administration of George Bush chose not to appeal the decision to the Supreme Court.
• Many Americans are unaware that the use of asbestos is still permitted in the USA.
Effort to ban asbestos in the USA
Bruce Vento Ban Asbestos and Prevent Mesothelioma Act of 2007 - Amends the Toxic Substances Control Act to require the Director of the National Institute for Occupational Safety and Health to conduct studies and report on the health effects of non-asbestiform minerals and elongated mineral particles.
Requires the Administrator of the Environmental Protection Agency (EPA) to establish a plan to: (1) increase awareness of the dangers posed by asbestos-containing materials and products and contaminants in homes and workplaces and by asbestos-related diseases; (2) provide information to, and encourage participation in research and treatment endeavors by, asbestos-related disease patients and their families and front-line health care providers; and (3) encourage health care providers and researchers to provide to patients and their families information relating to research, diagnostic, and clinical treatments relating to asbestos.
Requires the Administrator to promulgate regulations that prohibit the importing, manufacturing, processing, or distributing of asbestos-containing materials, subject to limited exemption upon petition and specified exemptions sought by the Department of Defense (DOD) and the National Aeronautics and Space Administration (NASA). States that such prohibitions do not apply to specified diaphragm electrolysis installations.
Requires the disposal of asbestos-containing materials within two years. Exempts products that are no longer in the stream of commerce or that are in the possession of an end user.
Amends the Public Health Service Act to: (1) direct the Secretary of Health and Human Services to expand and coordinate research programs on diseases caused by asbestos exposure, particularly mesothelioma, asbestosis, and pleural injuries; (2) provide for establishment of a national clearinghouse for data and specimens relating to asbestos-related diseases; (3) require the Director of the National Institutes of Health (NIH) to establish an asbestos-related disease research and treatment network; and (4) direct the Secretary to support research on mesothelioma and other asbestos-related diseases that is directly relevant to the health of the Armed Forces.
Bruce Vento Ban Asbestos and Prevent Mesothelioma Act of 2007August 2, 2007