Natural Diabetes Cure and Treatment

Reverse Diabetes Now

Reverse Your Diabetes Today by Matt Traverso can be described as comprehensive eBook that reveals what can you do to reverse diabetes, what can you eat to reverse diabetes and what can reverse type 2 diabetes and part 1 diabetes conditions by natural means with 3 short weeks or fewer. Reverse Your Diabetes today is presented especially for those who are experiencing difficulty with their blood sugar levels. You will learn the real root causes of this condition, truth about germs, and how to improve the quality of our cells with a lot of useful nutrition tips. Finally, what people will learn, of course, is a concrete treating plan for diabetes that helps to kick the disease out of your body once and for all. In fact, this treatment is very simple, but it can stop your anxiety about diabetes effectively and fast! Best of all, the step-by-step, done-for-you system inside Matt Traverso's Reverse Your Diabetes Today guide works without harmful drugs, needles, expensive treatments, or awful side effects. This exact same process can also greatly reduce your need for insulin if you have Type 1 diabetes. Read more here...

Reverse Diabetes Now Overview

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This book comes with the great features it has and offers you a totally simple steps explaining everything in detail with a very understandable language for all those who are interested.

Overall my first impression of this ebook is good. I think it was sincerely written and looks to be very helpful.

Isobutylcyanoacrylate InsulinPeptides

Polyalkylcyanoacrylate or isobutylcyanoacrylate nano-capsules were used as a drug carrier also for oral administration 12, 13, 806-809 or enteral absorption 810 of insulin. The mechanism of formation of nanoparticles and nanocapsules of polyisobutyl-2-cyanoacrylate was studied 811 . The absorption of insulin was studied by measuring fasting glycemia in streptozotocin-induced diabetic rats after a single administration of encapsulated insulin (100 units kg-1 ) at various sites along the gastrointestinal tract 810 . The influence of sulfur dioxide and pH on the preparation and characterization of polyalkylcyanoacrylate nanoparticles was investigated 812 . Oral administration of insulin incorporated into the wall of isobutylcyanoacrylate nanocapsule to diabetic rats induces a long-lasting normalization of their fasting glycemia. The biological action of encapsulated insulin on DNA and glycogen syntheses in Chinese hamster ovary cells transfected with the human insulin receptor gene was...

Diabetes Research Continues

Other groups are also developing new tools to treat diabetes. In one study, researchers were able to bond insulin molecules and sugar-sensitive proteins to a biodegradable polymer. The polymer nanopar-ticles are injected into a repository under the skin. The nanoparticles can detect a diabetic's glucose levels and release appropriate amounts of insulin to keep blood sugar levels steady. The research indicates that diabetics could administer the treatment with only one daily injection, rather than the several pinprick glucose tests and then followed up with insulin shots. An injection a day is all that will be needed. No blood testing. No multiple injections. Tattoos for Diabetes Scientists are developing a smart tattoo that could tell diabetics when their glucose levels are dangerously low. Once perfected, the tattoo will allow glucose levels to be monitored around the clock, and could warn the patient if their glucose levels are too low.

Diabetes And Nanotechnology

Glucose is the primary source of energy in the human body. This simple sugar comes from digesting carbohydrates into a chemical that the human body can easily convert to energy. But, when glucose levels in the bloodstream are not properly regulated, a person can develop a serious condition known as diabetes. What happens is that the sugar (glucose) builds up in the blood instead of going to the cells. The American Diabetes Association estimates that 17 million people in the United States have diabetes, but that one-third are unaware they have the disease. Diabetes, says the American Diabetes Association, is a chronic disease that has no cure. People with diabetes must check their blood sugar levels several times a day to help keep their diabetes under control. For many of the million people diagnosed with diabetes, their daily orders are blood glucose levels. To control their glucose levels, patients with diabetes must take small blood samples many times a day. Such procedures are...

Nanorobots and Diabetes

One research group is developing the potential of using nanorobots for treating diabetes. The nanorobots use embedded nanobiosensors in the body to monitor blood glucose levels. The special sensors provide signals to mobile phones carried with the patient. If the glucose level is too low, the nanorobots activate a programmed tune in the cellular phone. The tune alerts the patient to take any necessary action regarding the diabetes. This potential use of the nanorobots may be more convenient and safe for data collection and patient monitoring.

What is the conventional way a person living with diabetes uses to measure and monitor his or her glucose level

Typically a person with diabetes, and depending on the severity of the disease, should sample his or her glucose level at least twice a day. And that is the minimum. Typically it is done 3 to 5 times a day once when you get up, once after breakfast, once after lunch, and once after dinner, and finally once before bedtime. The more often you monitor your readings, the better control you have on the disease. However, the more you monitor, the more painful the process can be for many people with diabetes. Remember you are sticking a needle in your finger to draw blood and there is always going to be pain associated with this approach. And one of the big issues related to diabetes control is that many people, because of the pain, will not sample themselves the number of times they should in order to control their diabetes. Then after getting a blood sample, and depending on the glucose reading, a person would inject insulin, if needed. And this can occur after each glucose reading.

The Story of Biotechnology

Boyer and Cohen's success in inserting a gene into bacteria aroused the interest of a young venture capitalist, Robert Swanson, from San Francisco. In 1976, Swanson's question was, how could the Boyer-Cohen technology be used to produce a marketable protein product, perhaps a therapeutic product such as human insulin In April of that year, Swanson and Boyer each invested 500 to create Genentech, the world's first biotechnology company. Competition quickly followed, with the formation of Biogen. The flag of the biotech industry had been planted, and the first goal was to create human insulin. Genentech and Biogen chose different technical paths to this common goal. Genentech focused on chemically synthesizing the human insulin gene, whereas Biogen relied on cloning techniques. The chemically synthesized gene would escape the NIH safety regulations, but the cloning of the human gene would be subject to the NIH controls. At the time, Genentech was a company in name only. It had no staff,...

The Future of Nanotechnology

Only scientists armed with a sound understanding of the fundamental principles are likely to explore, discover, and invent. They will be questioned and challenged every step of the way. Such was the case with Riggs, Itakura, and Boyer in the example of synthetic insulin. Somatostatin was an experiment of high potential and promise to the City of Hope scientists, and yet even the expert reviewers at the National Institutes of Health failed to recognize the value of the Riggs-Itakura grant proposal. Boyer, well versed in the science, understood the logic and so was able to sell the idea to Swanson. This secured financial support for the somatostatin experiment based on the promise that it provided the pathway to insulin. And so it did.

Wireless Medical Monitor Advantages and Disadvantages The Concept

A wireless physiological measurement system measures in real-time, a bio-signal for local processing (Hao and Foster 2008). A good example is an automatic internal cardiac defibrillator (AICD, also known as an implantable cardioverter defibrillator or ICD), which acts to restore the regular heart rhythm by delivering an electric shock if abnormal behavior is detected, potentially averting sudden cardiac death (Hao and Foster 2008). Another example is implantable drug delivery systems, which deliver medication more efficiently for chemotherapy, pain management, diabetic insulin delivery, and AIDS therapy, by locally processing wireless physiological measurements (Jones et al. 2006). Monitoring chronically ill patients with heart disease, diabetes, and epilepsy

Nano Interview Professor Makarand Mak Paranjape PhD Georgetown University

In developing a biosensor that detects glucose levels in patients with diabetes. Dr. Paranjape and a team at Georgetown University and Science Applications International Corporation (SAIC) have developed a biosensor micro-device that has the potential to be used by people who have diabetes. The biosensor is in the form of a small adhesive patch to be worn

In VitroIn Vivo Studies

The nanoparticles are colloidal polymeric drug carriers that hold promise for peroral drug delivery. The peroral administration of nanoparticles was reviewed 940 . Nanoparticles were retained in the gut of rats and mice in small quantities for substantial time periods (up to 6 days). They were taken up in particulate form in the intestine and appeared in the lymph nodes, blood, liver, spleen, and sites of inflammation in the body. Three possibilities in the mechanism of uptake were discussed (1) intracellular uptake (2) intercel-lular paracellular uptake and (3) uptake via the M-cells and Peyer's patches in the gut. The uptake was size-dependent smaller particles were taken up to a higher degree than larger particles. Binding to nanoparticles enhanced the peroral bioavailability of a number of drugs, and a significantly enhanced and prolonged pharmacological activity by binding to nanoparticles was reported for insulin and hydrocortisone. The contribution of Francis Puisieux and his...

FDA Preparation For Acquiring Expertise in Emerging Technologies

The FDA was able to equip itself for effective regulation of early biotechnology products. The biotechnology revolution was launched in 1976 when a human protein was expressed from recombinant DNA in E. coli. Recombinant DNA technologies resulted in products such as synthetic insulin to treat diabetes and interferon to treat leukemia, and the biotechnology industry began to take flight in the 1980s. The FDA responded to the emerging industry in several ways. First, the FDA decided not to create a new Center for biotechnology, but to incorporate biotechnology products into the current regulatory structure.70 Each product was regulated on a case-by-case basis for safety and efficacy. The Office of Biologics Research and Review (OBRR) became the FDA's expert in biotechnology review. OBRR hired specialists in molecular biology, protein chemistry, and immunology almost all biotechnology products, including drugs and devices, were sent to OBRR

Concept 1 Lessons From the SCurve

In the case of biotechnology, the original S-curve might be characterized as the technology for commercialization of animal proteins for human use, as in the case of insulin. Bovine and porcine insulin were extracted from slaughterhouse animals and then purified and sold. The discontinuity created by the second S-curve involved the use of the synthesized insulin gene inserted into bacteria for the production of human insulin. This innovation provided the basis for an entirely new industry.

Properties and Functions of Bone

Between the ends of the molecules and pores between the sides of parallel molecules (Vigier et al. 2010 Zhu et al. 2005 Miyahara et al. 1984). The collagen fibers provide the framework and architecture of bone, with the HA particles located between the fibers. Noncollagenous proteins, for example, growth factors and cytokines (such as insulin-like growth factors and osteogenic proteins), bone inductive proteins (such as osteonectin, osteopontin, and osteocalcin), and ECM compounds (such as bone sialoprotein, bone proteoglycans, and other phospho-proteins as well as proteolipids), provide minor contributions to the overall weight of bone but provide large contributions to its biological functions. During new bone formation, noncollagenous proteins are synthesized by osteoblasts, and mineral ions (such as calcium and phosphate) are deposited into the hole-zones and pores of the collagen matrix to promote HA crystal growth. The ground substance is formed from proteins, polysaccharides,...

Drug Delivery Applications Of Nanogels

The strategies that are being pursued are active targeting by modifying and func-tionalizing the surface of nanoparticle with tissue-specific antibodies or ligands. In passive targeting, the advantage of leaky vasculature associated with inflammatory milieu or in tumor is explored. However, the challenge in targeting is that nanoparticles attract the natural body defense system and hence are easily identified and taken up by the reticuloendothelial system. Therefore, successful nanostructure design requires assembly of appropriate surface characteristics as well as targeting ligands to achieve long systemic circulation and subsequent interactions with the receptors in the target tissue 245 . Nanogel formulations provide a better platform for designing of nanocarri-ers because of their three-dimensional cross-linkage structure with hydrophilic surface properties that prevent their clearance by the reticuloendothelial system. In addition, nanogels demonstrate unique properties, such as...

Mems Devices For Biomedical Applications

The development of new, affordable, disposable analytic microchips is changing diagnostics. Examples of analytical functions that are benefiting from such developments include blood supply screening, analysis of biopsy samples and body fluids, minimally invasive and non-invasive diagnostic procedures, rapid identification of disease, and early screening. These systems will eventually perform diagnostic procedures in a multiplexed format that incorporates multiple complementary methods. Ultimately, these systems will be combined with other devices to create completely integrated analysis and disease-treatment systems. There are a number of mechanisms to provide timed release of drugs, such as micro-encapsulation and transdermal release (discussed earlier). Implantable Bio-MEMS are preferred for therapies that require several daily injections, such as for diabetes treatment. If the drug level is monitored in real time, it could also be adapted to metabolic

Catalysis Greening the Pharma Industry

In a regulated industry where products and processes must be validated prior to receiving marketing approval it is much more difficult to change the process post-launch. Thus, by the time of product launch, the pharma industry aims to have already applied green chemistry practices wherever possible to minimize waste and environmental impact and to reap the benefits of that process from day one of the launch 4 . The German manufacturer Merck, for example, has developed a new process for producing sitagliptin-the active ingredient in Januvia, a drug for type 2 diabetes-that reduced the waste per kilogram of sitagliptin manufactured by 50 , and completely eliminated aqueous waste streams. The concept is general new chemical industrial processes may now be conducted in a one - step, solvent-free manner, minimizing consumption of energy, pro-

Nanotechnology Videos and Audios

Monitoring Blood Glucose Without Pain or Blood. A short film of Professor Paran-jape and the lab where the diabetes biosensor device is produced. http college. What are the Symptoms of Diabetes Who is at Risk How is Diabetes Confirmed Diabetes Clinic. IrishHealth. (56K Dialup. http www.irishhealth.com clin diabetes video.html

Red and green biotechnology

Traditionally, red biotechnology is the term applied to medical processes, producing drugs such as insulin, dornase alpha, and In the past, distinguishing agricultural applications from medical applications of rDNA technologies has been relatively easy, as it is a simple matter to draw a line between, for example, herbicide-tolerant soybeans and insulin. But recent innovations have blurred this simple dichotomy. Most vitamin C tablets are now synthesized from corn, and over half the US corn crop is of genetically engineered varieties. The fact that the chemical composition of the vitamin C is identical, whether coming from genetically engineered corn or traditional corn, is irrelevant, because we are dealing with ethical issues of the use of rDNA. The point here is that vitamin C cannot be readily assigned to the (ethically acceptable) medical or the (ethically unacceptable ) food category. Other products of rDNA applications are similarly obscured foods with enhanced nutrient content...

Polyisobutylcynoacrylate Nanocapsules

Intragastric administration of insulin-loaded poly(isobutyl-cyanoacrylate) nanocapsules induced a reduction of the glycemia to normal level in streptozotocin diabetic rats 80 and alloxan induced diabetic dogs 81 . The hypol-glycemic effect was characterized by surprising events including a lag time period of 2 days and a prolonged effect over 20 days. Insulin is a very hydrosoluble pep-tide and should be inactivated by the enzymes of the gastrointestinal tract. Thus, that insulin could be encapsulated with high efficiency in nanocapsules containing an oily core and why these nanocapsules showed so unexpected biological effect remained unexplained. Nanocapsules were prepared by interfacial polymerization of isobutylcyanoacrylate 82 . Any nucleophilic group including those of some of the aminoacids of insulin 83 could initiate the polymerization of such a monomer. In this case, insulin could be found covalently attached to the polymer forming the nanocap-sule wall as was recently...

Gas Phase Sensor Arrays Electronic Noses

Although food analysis has been the most explored field of application for electronic noses, more recently the medical field was also taken into consideration and the application of the electronic nose to detect diseases was proposed 133-136 . The hypothesis of these studies was that body odor is correlated with human health. Human odor is in fact correlated with the combined action of both gland and bacterial population and any change of the complex equilibrium regulating the organism can induce a change in the nature and amount of volatile organic compounds excreted by the organism. On the other hand medicine recognizes that some pathologies produce unpleasant characteristic odors (for example diabetes and hepatic diseases). As a consequence the exploitation of electronic nose, which is a noninvasive probe, can represent an eligible tool for a preliminary diagnosis of diseases. In particular, the sensor array was able to detect 5a-androst-16-en-3-one, a steroid present in human...

Present and future applications of nanotechnology

No one has yet invented a little machine that will swim through your body and mechanically strip away plaque from your inner arterial walls nonetheless, nanotechnology is poised to have an enormous impact on the diagnosis and treatment of disease. Recall that one of the Grand Challenges of the NNI is the ability to detect cancerous tumours that are only a few cells in size. Medical imaging could be vastly improved by using nanoparticle-based materials to enhance the optical contrast between healthy tissue and diseased tissue. Diabetes treatment could be improved by injecting a nanoparticle into the blood that automatically delivered a dose of insulin upon sensing an imbalance in blood glucose level. Cancer may be treated someday soon with an injection of nanoparticles that latch onto cancerous tissue and cook it to death upon external application of a light source that poses no threat to healthy tissue.

Applications of biotechnology

The first was the commercialization of an example given above, the transfer to a bacterium of a human gene for insulin, to produce human insulin. Today, the majority of insulin used by diabetics is genetically engineered and produced by bacteria, instead of extracting insulin from farm animals. Other applications followed quickly, including a wide range of pharmaceuticals, foods, and crops. The first commercial food application was chymosin, a genetically engineered enzyme used in cheesemaking and produced by bacteria as an alternative to rennet, which comes from animal sources. The development of genetically engineered chymosin allowed true vegetarian cheeses and also, like insulin, saved unnecessary slaughter of farm animals.

Tissue Engineering Scaffolds

Polymeric nanofiber matrix has similar structure to nanoscaled nonwoven fibrous ECM proteins, and thus is a wonderful candidate for ECM-mimic materials 4 . In recent years, the ease of polymer nanofiber fabrication using electrospinning began to stimulate more and more researchers to explore the application of nanofiber matrix as a tissue engineering scaffold 5-8 . A successful tissue engineering scaffold should have cell-compatible surfaces to allow cell attachment and proliferation. Based on the understanding of the biorecognition mechanism 9 of the interaction between cells and biomaterial surfaces, most research work to improve biocompatibilities of polymeric tissue engineering scaffold center on immobilization of biomolecules that can be specifically recognized by cells on the biomaterial surfaces. These biomolecules include adhesive proteins such as collagen, fibronectin, RGD peptides, and growth factors such as bFGF, EGF, insulin, and the like. The biomolecules can either be...

The Regulatory Approval Issues That Nanotechnology Presents

Nanotechnology will present a host of complicated issues related to regulatory approval. Nanomaterials and devices will primarily be used to develop more advanced versions of a number of existing products. There will be many uncertainties and questions associated with what amounts of additional data will be required to obtain regulatory approval. For example, the novel drug delivery techniques resulting from nanotechnology will present challenging data issues. As discussed in Chapter 1, examples of drug delivery mechanisms include the use of nanostructures that release traditional antibiotics only when near an infection, coatings that prevent digestive enzymes from breaking down the drug in the stomach, and implantable devices that can periodically dispense medicines, such as insulin or morphine. When a new drug delivery system is used in conjunction with a drug that has NDA approval, the FDA will be forced to make difficult decisions about the risks of the new therapy and the data...

Field Effect Transistor Biosensors

Carbon nanotubes also have excellent mechanical properties and chemical stability in addition to potentially tunable electrical properties, making them highly desirable electrode nanoelectrical materials for any number of nanoelectrical applications 10.84 . Biomolecules can be bound to carbon nanotubes, particularly in FET and nanoelectrode applications. Most biomolecules bound to carbon nanotubes are not cova-lently bound (as discussed above) and do not exhibit direct electrical communication with the nanotube, though redox enzymes bound to nanotubes and other conductive nanomaterials may 10.84, 85 . Flavin adenine dinucleotide (FAD) and flavoenyzme glucose oxidase (Gox) both display quasi-reversible one electron transfer when absorbed onto unannealed carbon nano-tubes in glassy carbon electrodes. Gox so immobilized retains its substrate-specific (glucose) oxidative activity, leading to applications in sensing circulating glucose for diabetes and, perhaps, to a strategy of harvesting...

Drug Transport Vectors

One approach to improve brain tumor uptake of boron compounds has been to conjugate them to a drug-transport vector by means of receptor-specific transport systems.160,161 Proteins such as insulin, insulin-like growth factor (IGF), TF,162 and leptin can traverse the BBB. BSH encapsulated

From Treating Disease To Establishing Health

Medical researchers now study diseases, often seeking ways to prevent or reverse them by blocking a key step in the disease process. The resulting knowledge has helped physicians greatly they now prescribe insulin to compensate for diabetes, anti-hypertensives to prevent stroke, penicillin to cure infections, and so on down an impressive list. Molecular machines will aid the study of diseases, yet they will make understanding disease far less important. Repair machines will make it more important to understand health.

Experiment in the Palm of Your Hand Labona Chip

By using these approaches to move fluids among the mixing elements and reactors, it is possible to control interactions precisely, and the lab-on-a-chip has already become reality. Companies like Affymetrix (with their product GeneChip) and Agilent (with their product LabChip) make lab-on-a-chip devices for genetic analysis. It is hoped that these chips may develop to the point where they can be used for point-of-care applications so that a doctor can give a patient an immediate analysis of blood or any other samples that the doctor takes. They may also be used for drug delivery, particularly in cases where drugs need to be dispensed over a long period of time in response to changing body chemistry (as in diabetes, for example). In the more distant future, it is possible that lab-on-a-chip might serve as a framework for DNA computing since early experiments in that field operate in just microliters (a millionth of a liter) of solution but require large-scale analysis of results to be...

Magnesium in the Body

Absorption of magnesium occurs in the upper small bowel by means of an active process closely related to the transport system for calcium. Magnesium is excreted mainly by the kidney. Renal excretion of magnesium increases during diuresis induced by ammonium chloride, glucose, and organic mercurials. Magnesium affects the central nervous, neuromuscular, and cardiovascular systems. Insufficient magnesium (hypomagnesemia) in the extracellular fluid increases the release of acetylcholine and can cause changes in cardiac and skeletal muscle. Some of the conditions that can produce hypomagnesemia are diarrhea, steatorrhea, chronic alcoholism, and diabetes mellitus. Hypomagnesemia may occur in newborns and infants who are fed cow's milk or artificial formulas, apparently because of the high phosphate magnesium ratio in such diets. Hypomagnesemia is often treated with parenteral fluids containing magnesium sulfate or magnesium chloride. Excess magnesium (hypermagnesemia) in the body can slow...

Nanoscale Power Plants

For the more than 100 million people worldwide who have diabetes, testing their blood glucose level is the only way to be sure that it is within normal range and to adjust the insulin dose if it is not. The current method for monitoring blood glucose requires poking a finger to obtain a blood sample. The equipment needed to perform the blood test includes a needle device for drawing blood, a blood glucose meter, single-use test strips, and a log book. Now imagine this scenario your doctor implants a tiny device the size of a rice grain under your skin. This device automatically and accurately measures your blood glucose levels at any desired interval, even constantly if required. It transmits the data to an external transceiver. If any abnormality is detected, the device warns you and automatically transmits the data to your doctor's computer. This scenario is one of the many promises of nanomedicine where in situ, real-time, and implantable biosensing, biomedical monitoring, and...

Nanotechnologybased Stem Cell Therapies for Damaged Heart Muscles

Regenerative medicine is an area in which stem cells hold great promise for overcoming the challenge of limited cell sources for tissue repair. Stem cell research is being pursued vigorously in the hope of achieving major medical breakthroughs. Scientists are striving to create therapies that rebuild or replace damaged cells with tissues grown from stem cells, offering hope to people with cancer, diabetes, cardiovascular disease, spinal cord injuries, and many other disorders.

Pharmaceutical Nanotechnology Research

The need for new or improved medicines in several therapeutic areas will lead to the increasing use of nanotechnology in pharmaceutical applications. These areas include protein-based compounds for cancer, diabetes, and for infectious diseases. Experts also predict that over the

Implantable devices including sensing devices implantable medical devices and sensory aids

Implantable sensors can be engineered to work with medical devices to automatically administer treatments for a variety of conditions. Implantable microfluidic systems are being developed to dispense drugs on demand. Initial applications of these systems will likely include delivery of chemotherapy drugs for oncology patients and the delivery of drug treatments for patients suffering from a variety of diseases including, autoimmune disorders, human immunodeficiency virus acquired immunodeficiency syndrome (HIV AIDS) and diabetes. Implantable sensors that monitor heart rate can also act as a defibrillator to regulate irregular rhythms.

Mining the Medical Possibilities of Nanotechnology

Nanospectra Biosciences (www.nanospectra.com) is one company pushing the envelope in nano-medical applications today. They have patented nanoshell particles used in noninvasive medical therapies. These nanoparti-cles can actually be tuned to scatter or absorb light in specific wavelengths. This makes possible tasks such as destroying specific cancer cells with an infrared laser, welding tissues to heal wounds, and something called photocoagulation (coagulation with a laser) that cuts off the blood supply to unhealthy cells, slowing down degeneration in people with diseases such as diabetes and cancer.

Biocompatibility Of Nanoporous Membranes And Biocapsular Environment

The behavior of different cell types in three-dimensional silicon microstructures was studied using microfabricated half-capsules 10 . All cells had normal growth characteristics, morphology, and greater than 90 viability. Overall, islets in microfabricated silicon pockets and the control dishes appeared to have similar morphology and viability. Glucose-supplemented medium was allowed to diffuse to the islets, from underneath the membrane, to stimulate insulin production and monitor cell functionality. The concentration of insulin, secreted by the islets through the membrane, into the surrounding medium was compared

Matrix Materials Inside The Biocapsule

Oxygen is known to be a critical factor that influences insulin secretion by islets. The diffusional limitations imposed by a biocapsule construct can potentially make it a hy-poxic environment for the cells. In the attempt to partially overcome this constraint, cells were seeded in various extracellular matrix materials within the biocapsule. Their behavior was compared with free cells, which form aggregates. We showed that the addition of a matrix, particularly alginate or collagen, within the micromachined biocapsule proved to augment the functionality islets in microfabricated biocapsules 62 (Figure 10.10). Supporting our studies, Tatarkiewicz et al. also demonstrated that the use of alginate three-dimensional matrix allowed cell clusters to be cultured at least two times higher density compared with culture in suspension. The clusters immobilized in a matrix resulted with 3-fold increase in insulin content and 9-fold increase in insulin DNA ratio 58 . This suggests the importance...

Implantable Drug Delivery

Nanoporous membranes are microfabricated with well-defined pores (diameters in the tens of nanometers). The membranes can be used to deliver small-molecule, peptide, or protein drugs (Figure 16-5). One application under investigation involves encapsulation of pancreatic islet cells for insulin delivery. The reproducible and uniform pore size precisely controls the material exchange across nanoporous membranes Nutrients for the cells and secreted insulin can pass through the pores, but proteins and cells from the immune system that may attack the implanted islet cells are restricted from entering the biocapsules due to their size.

Lowfrequency Sonophoresis

Low-frequency sonophoresis has been a topic of extensive research only in the last 10 years. Tachibana et al. 60-62 reported that application of low-frequency ultrasound (48 kHz) enhanced transdermal transport of lidocaine and insulin across hairless rat skin in vivo. They found that the blood glucose level of a hairless rat immersed in a beaker filled with insulin solution (20 U ml) and placed in an ultrasound bath (48 kHz, 5000 Pa) decreased by 50 in 240 minutes 62 . They also showed that application of ultrasound under similar conditions prolonged the anesthetic effect of transdermally administrated lidocaine in hairless rats 61 and enhanced transdermal insulin transport in rabbits. Mitragotri et al. 8, 43 showed that application of ultrasound at even lower frequencies (20 kHz) enhances transdermal transport of various low-molecular weight drugs including corticosterone and high-molecular weight proteins such as insulin, y-interferon, and erythropoeitin across the human skin in...

Therapeutic Microsystems

Therapeutic microsystems are designed to alleviate certain symptoms and help in the treatment of a disease. In this category, we will describe two such microsystems. The first one is a drug delivery microchip designed to administer small quantities of potent drugs upon receiving a command signal from the outside. The second device is a passive micromachined glucose transponder, which can be used to remotely monitor glucose fluctuations allowing a tighter blood glucose control through frequent measurements and on-demand insulin delivery (pump therapy or multiple injections)

Influence of Enzymes on the Stability of Poly Alkyl Cyanoacrylate Nanoparticles

The peroral route is the most convenient way of delivering drugs, leading to better patient compliance, especially during long-term treatment. However, many drugs, including proteins and peptides, are unstable in the gastrointestinal tract (GIT) or are insufficiently absorbed. Earlier studies have shown that cyanoacrylate nanoparticles58,59 and nanocapsules60,61 improve the absorption of several drugs like vincamin or insulin from the GIT. Maincent et al.58 demonstrated the efficiency of PBCA nanoparticles as a drug delivery system for the GIT by improving the absorption of vincamin by more than 60 compared to an equimolar solution. Investigation of the parameters that influence the stability of nanoparticles in the GIT is much more difficult because of the complexity of the GIT. The pH changes from 2.0 in the stomach to 7-8 in the small intestine. Moreover, in different parts of the GIT there are different enzymes in differing concentrations. Degradation studies with cyanoacrylate...

Mobility is Important for Cellular Function

Classical examples are receptor tyrosine kinases such as insulin and EGF receptors (Schlessinger 2000). There are an increasing number of recent reports indicating that seven-transmembrane-helix (7TM) receptors (also named G protein coupled receptors, GPCRs) also form homo- and heterodimers whose functional importance is presently a matter of debate (Bulenger et al. 2005 Chabre and le Maire 2005). The role of diffusing neuroreceptors for development and plasticity of synaptic transmission was demonstrated using single particle imaging by Choquet and Triller (2003).

Biomedical Properties 61 Introduction

The pioneers in this field discovered that the nano-capsules could be used as new type of lysosomotropic carrier 6, 7 , as new dosage forms 2, 655 , or for controlled release of drugs 1 . Early work also focused on the preparation and characterization of hemolysate-loaded poly(N-a, N-e-L-lysinediylterephthaloyl) 3 , gelatin 4 , and poly-isobutylcyanoacrylate nanocapsules 8-10, 656 . It was found that the polyalkylcyanoacrylate nanocapsules increased the intestinal absorption of a lipophilic drug 5, 11 . Since the mid 1980s, many different active molecules, such as anti-inflammatory agents, anticancer drugs, immunostimulating compounds, anti-infectious agents, antiglaucomatous drugs, and even peptides have been encapsulated and as a result their pharmacological effect has been improved or their secondary effects reduced compared with free drugs after administration by oral, parenteral, or ocular routes. The nanocapsules have been found also to be suitable as a biodegradable drug...

Nanotechnology Fights Infections

The antibacterial and antiviral properties of silver are found in the products of other industries as well. One shoe manufacturer is using silver fiber built into shoes to prevent foot fungus and bacteria from growing. This is important to diabetics, as they are prone to serious foot infections such as gangrene, which can result in amputation of the foot or limb if infection is allowed to set in.

Wawa Vavava

To produce bioactive proteins, CAD moieties must be removed. Rivera et al. solved this problem by interposing a furin cleavage sequence between therapeutic protein and the CAD. In one example, Rivera et al. (2000) demonstrated that a natural version of hGH could be secreted in a controllable fashion using disaggregator technology. Thus, a single amino acid change (Phe36 to Met) converted monomeric FKBP12 into a CAD. Recombinant hGH was generated via a cDNA construct (Fig. C.3) consisting of a CMV promoter, signal sequence, four CAD motifs, a furin cleavage signal, and growth hormone (proinsulin was also used). Vectors were stably transfected into HT1080 cells and fluorescence microscopy was used to demonstrate ER retention of both insulin and growth hormone in the absence of disaggregator. Cells expressing fusion proteins were then treated with increasing concentrations of disaggregator for 2 hours. The authors showed that accumulated protein was released by disaggregator...

Summary

B) One may see enormous improvements in patient care pathways. For diabetes and other endocrinopathies, the standard of care may change from multiple daily injections to a single injection of gene therapy followed by ingestion of multiple tablets each day. Drug therapy could truly be personalized once individual disease patterns are established (e.g., via sensor technology), the patient and physician could work together to develop a rational, personalized regimen of small molecule administration that would be expected to yield improved compliance and better control of disease this in turn should lessen the cost of disease to U.S. society.

Biosensors

Glucose detection is a classic problem in biosensing. Diabetics cannot control their insulin levels therefore, their levels of blood glucose fluctuate tremendously. If those levels get either too high or too low, their conditions can be life threatening. Currently, most Type I diabetics must actually draw blood on a daily basis, or even more often, to test for blood glucose levels. Sensing glucose molecules can be done in many ways, using optical, conduction, or molecular recognition methods. None of these have yet been shown to be compatible with an implantable simple device that could automatically, continuously sense the glucose levels in the blood. This is one of the major challenges for chemical sensing, and nanoscale structures may advance it very substantially.

Alternatives

But the Companion's technology may be delivered in other ways. One possible configuration would be similar to a pocket calculator with a foldout viewing screen, similar to Apple's Newton. Or the Companion could be designed as an implant, inserted into the body, powered by blood sugar, and connected directly to visual and auditory nerves. Assuming it will be harder to work out these biological details than to use known technologies for visual displays, audio, and so forth, an implant version of this technology while inevitable seems further in the future.

Nanopores

Nanopores are essentially nanoparticles whose surface contains pores, which can be used for containing drugs. Uniformly spaced holes are created on the surface in which a drug molecule is contained. The pore size imposes a restriction on the size of the biomolecules present. This means that small molecules like oxygen, glucose, insulin, neurotransmitters, etc. can move across the pore surface while large immune system molecules like immunoglobulin cannot. The released molecule can therefore be used in disease treatment, e.g. the use of insulin in diabetes treatment, use of neurotransmitters in neural disorders, etc. (Refs 9, 10).

Biochips

Glucose sensors are probably the most well known biosensors on the market today, since thousands of people with diabetes must be able to monitor their glucose levels throughout the day. Glucose can be tested by using the enzyme glucose oxidase, which combines glucose and oxygen to form gluconic acid and hydrogen peroxide. The sensor detects the amount of hydrogen peroxide formed and current changes that are measured by an electrode.

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When the cell machinery reads gene 3, it follows the recipe by finding a methionine floating around the cell, and connects to it an alanine molecule. The next word, CAA, calls for glycine, so the cell finds and attaches a glycine molecule to the methionine and alanine already connected, thus building an elongating chain of designated amino acids. An average gene is about 1000 bases long, or 330 genetic words, which means a protein chain consisting of about 330 amino acids. The particular sequence of amino acids gives the protein its particular features, which in turn give the cell and ultimately, the organism, a particular trait. Some proteins are very short, simple chains of amino acids, others are long, complex, composed of several amino acid chains or are further modified prior to activation. Human insulin, for example, is a fairly simple protein composed of two amino acid chains, one is 30 amino acids long, the other 21 amino acids long. (Many other animals...

Oral Delivery

Insulin The oral delivery of the peptide insulin is a very important and yet unresolved issue in medicine since by this route of administration the presently necessary frequent injections can be avoided. Insulin is rapidly degraded in the gastrointestinal drug and therefore cannot be given in conventional oral dosage forms. Insulin can be encapsulated into poly(isobutyl cyanoacrylate) nanocapsules particles by the interfacial polymerization method described in Section 4.2 101-103, 358-361 . The oral administration of these nanoparticles decreased glycemia in diabetic rats fasted overnight before dosing by 50-60 103 . This effect lasted up to 20 days. Nonencapsulated insulin had no effect. In fed diabetic rats the nanoparticles yielded a 25 reduction in blood glucose levels only at high doses. Administration to different locations in the intestine exhibited a dependence of the glycemia on the administration sites leading to 65 glycemia after administration into the ileum, 59 for...

Polyo iLactide

Although the oral route for insulin delivery is the most convenient, directly administered oral insulin is degraded by proteolytic enzymes in the gastrointestinal (GI) tract. Polylactide was prepared in order to microcapsulate the insulin to avoid the enzymes in the GI 872 . The poor selectivity of photosensitizers for tumor tissue remains a drawback in photodynamic therapy (PDT) and could be improved by adapted formulations. The cellular uptake,

Solvent Process

Nanoparticles nanocapsules or nanocomposites. Besides the solvent evaporation method, the emulsion techniques, such as partial-microemulsion, double-microemulsion, pressure homogenization-emulsification, or modified spontaneous emulsification solvent diffusion methods, can be categorized as solvent methods. The solvents used vary from water, to organic solvents, like acetone, ethanol, chloroform, benzene, 2-propanol, 2-methoxyethanol, 1,2-dimethoxyethane, N, N-diethylaniline, N, N'-dimethylformamide, trihexylamine, ammonium carbonate, ammonia solution, etc. The polymers, like poly(D,L-lactic acid), poly(N-vinyl-2-pyrrolidone), poly(lactide-co-glycolide), poly-2-caprolactone, poly(y-benzyl L-glutamate), poly(ethylene oxide), poly(ethylene glycol), etc., can be employed for this purpose, especially for coating the biomaterials. The solvent process has been used for encapsulation of not only metal nanoparticles, but also biomedical materials, such proteins, cyclosporin A, triptore-lin,...

Fluid Flow

The super small size of nanotubes allows them to pierce the skin painlessly (always a plus), especially for people who have to check their blood several times a day, such as Type II diabetes patients. TheraFuse, Inc., is an emerging technology company that designs and develops infusion systems for delivering pharmaceutical and biopharmaceutical liquids. Since 2001, TheraFuse has created products that measure various fluid flow rates during therapeutic drug infusion (e.g., very low insulin infusion rates for newborns to very high infusion rates needed for clinical intravenous drug delivery). Currently, the Vista, California, company is creating a skin patch for diabetic use. By using nanostraws to draw blood and check glucose levels and then inject insulin when needed, the diabetic patch will make the mechanics of the disease a lot easier, especially for children.

Porous Silicon

The attraction of placing active electronic circuit components into in-vivo drug delivery materials led to the exploration of elemental silicon as a biomaterial. In particular a porous form of Si produced by an electrochemical corrosion reaction has been of interest. Since the pioneering work of Canham and others in the late 90's demonstrating the biocompatibility and biodegradability of porous Si in vitro and in vivo 25-35 , this material has been under intensive investigation for controlled drug delivery applications. Like mesoporous silica of the MCM41 class, porous Si offers tuneable structural properties a large specific surface area, large free volume, and pore sizes that can be controlled from a few nanometers to several hundreds of nanometers depending on the preparation conditions. The surface of freshly prepared porous Si is easily modified via convenient chemistry with a large range of organic or biological molecules (ex antibody, proteins, etc.) 36 . Recently Swaan and...

Passive Micropumps

Nagakura et al. 9.71 have demonstrated a meso-scale osmotic actuator that converts chemical energy to mechanical displacement. Osmosis is a well-known phenomenon by which liquid is transported across a semipermeable membrane to achieve a uniform concentration distribution across the membrane. If the membrane is flexible, such as the one used by Nagakura et al. 9.71 , then the transfer of liquid would cause the membrane to deform and act as an actuator. The inherent drawback of using osmosis as an actuation mechanism is that it is a very slow process Typical response times (on a macroscale) are on the order of several hours. However, osmotic transport scales favorably to the microscale, and it is expected that these devices will have response times on the order of several minutes, rather than hours. Based on this idea, Nagakura et al. 9.71 are developing a miniature insulin pump. Su et al. 9.72 have demonstrated a mi-croscale osmotic actuator that is capable of developing pressures as...

Concluding Remarks

Nanocapsules are designed to have a therapeutic action to release drugs in the right place or to have functionality to attack and reduce cancerous cells. Although many applications have not been investigated yet, current developments are becoming increasingly more useful in the field of medicine. Nanocapsules have been intensively studied not only because of the possibilities for controlled release, but also because of increased drug efficacy and reduced toxicity after parenteral administration. The nanocapsules have been formulated into a variety of useful dosage forms including oral liquid suspensions, lotions, creams, ointments, powders, capsules, tablets, and injections. Nanoencapsulation has been applied to solve problems in the development of pharmaceutical dosage forms as well as in cosmetics for several purposes including conversion of liquids to solids, separation of incompatible components in a dosage form, taste-masking, reduction of gastrointestinal irritation, protection...

Peptide Delivery

Much of the research has focused on the absorption enhancement of peptide and protein drugs and vaccine antigens. Couvreur and co-workers have been studying whether nanoparticles composed of polyalkylcyanoacrylate derivatives enhance the absorption of orally administered insulin, using animal models 158-161 . They found that insulin encapsulated in polyisobutylcyanoacrylate nanocap-sules reduced glycemia by 50-60 , although free insulin did not affect glycemia when administered orally to diabetic rats. Kawashima et al. 162 reported that the absorption of elca-tonin, which is a calcitonin of eel, via the GI tract of rats was enhanced by poly(-lactide-glycolide) nanoparticles coated with chitosan, which is a mucoadhesive cationic polymer. They also studied the effect of chitosan-coated liposomes on the intestinal absorption of insulin in rats and reported that the blood glucose concentration decreased significantly after oral administration of insulin-loaded liposomes 163 . Sakuma et...

Bionanosensors

Bionanosensors are designed to pick up specific biological signals usually by producing a digital electronic signal associated with a specific biological or chemical compound. New methods such as micro nanofabrication as well as advanced electronics have made development of much improved biomedical sensors possible. These advanced biosensors have the ability to provide big changes in the medical, pharmaceutical, and environmental industries. Individual monitoring nanodevices such as glucose sensors for diabetics are also in development.

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