Nanotechnology Facilitates More Targeted Treatments


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Nanotechnology in Implantable

Medical Devices

 Topics Covered:

Introduction: What is Nanomedicine? Implantable Biosensors      Implantable Glucose Sensors Integration with Monitoring Systems      Chronic Disease Monitoring      Implantable Cardioverter-Defibrillators Implantable Drug Delivery Systems Regulatory Challenges Conclusions Sources

Introduction: What is Nanomedicine?

The term nanomedicine encompasses a broad range of technologies and materials. Types of nanomaterials that have been investigated for use as drugs, drug carriers or other nanomedicinal agents include:

  • Dendrimers
  • Polymers
  • Liposomes
  • Micelles
  • Nanocapsules
  • Nanoparticles
  • Nanoemulsions

Around 250 nanomedicine products are being tested or used in humans, according to a new report that analyzed evolving trends in this sector. According to experts, the long-term impact of nanomedicinal products on human health and the environment is still not certain.

During the last 10 years, there has been steep growth in development of devices that integrate nanomaterials or other nanotechnology. Enhancement of in vivo imaging and testing has been a highly popular area of research, followed by bone substitutes and coatings for implanted devices.

Active and passive cell targeting will continue to be an important focus in nanomedicine. Targeted nano-enhanced solutions have been shown to often enhance existing treatments, and some nanomedicinal techniques are being developed which work as diagnosis and treatment stages simultaneously.

The unknown factor as far as nanotechnology is concerned is whether the increased production, exposure and handling of products and nanomaterials will result in serious impact on the environment and humans. It is possible that toxicity will be the restricting factor for the public acceptance and commercial success of nanotechnology-based products.

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Advances in modern medicine are increasingly relying on electronic devices implanted inside the patient’s body. Nanotechnology allows us to create materials and coatings to construct these devices that are fully biocompatible. Image credit: NASA

Implantable Biosensors

Micro-electromechanical systems (MEMS) and silicon chips that are capable of implantation within the human body may permit interfacing semiconductor devices with living tissues.

Implantable Glucose Sensors

A molecular nanotechnology company Zyvex, specializing in MEMS, chose Diabetech LP as its medical device commercialization and development partner for their wireless sensor implant targeting real-time blood glucose levels in the body. Their novel portable device for patients does not only display the glucose levels from the implant to the patient but also conveys automatically in real time the information to GlucoDynamix, the clinical management system of Diabetech.

Likewise Digital Angel received a patent in October 2006 for their embedded biosensor system. A glucose-sensing RFID microchip is implanted in the patient. The chip can measure glucose levels precisely and can convey the same back to a digital scanner.

This will pave the way for implantable biosensors that can evaluate disease indicators or symptoms and regulate drug release to help in disease treatment.

For example, an implanted glucose sensor can be coupled with an insulin release system and help sufferers of diabetes control their sugar levels without the need for insulin injection or pin-prick tests.

While biocompatibility and long-term stability are being addressed, a number of prototypes have begun to emerge for the management of patients having acute diabetes or to treat epilepsy and other debilitating neurological disorders, and to monitor patients suffering from heart disease.

Integration with Monitoring Systems

Virtual Medical World published an article in November 2005 that stated that a research project financed by the Academy of Finland was underway to develop of minute subcutaneous sensors that can be used for active monitoring of the heart or prosthetic joint function even over long time periods.

For instance, a subcutaneous EKG monitor can detect cardiac arrhythmia, and this data can be wirelessly transmitted to the PC or mobile phone of the physician.

Chronic Disease Monitoring

Guidant is a specialist in treating vascular and cardiac disease and has invested in CardioMEMS based on an article published in Virtual Medical Worlds in November, 2005. CardioMEMS develops novel devices based on MEMS technology to help physicians monitor remotely the progress of chronic diseases like heart failure.

The University of Texas received a grant in 2006 to fund the research and development of an implantable intravascular biosensor that will monitor disease and health progression.

The nano pressure sensor can monitor pressure within the cardiovascular system while the data is transmitted to a wristwatch-like data collection device. The data is transmitted by this external device to a central remote monitoring station where it can be seen by health care providers in real time.

Implantable Cardioverter-Defibrillators

The implantable cardioverter-defibrillator (ICD) has transformed treatment of patients at risk for sudden cardiac death because of ventricular tachyarrhythmias.

The Medtronic CareLink Monitor is a small, convenient device that allows patients to gather information by holding an antenna over the implanted cardiac device. The data is automatically downloaded by the monitor and sent through an internet connection directly to the secure Medtronic CareLink Network. The patient’s data is accessed by clinicians by logging onto a website from any internet-connected computer in their home or office or through the laptop while travelling.

The ICD systems also include portable computer systems that program the implantable cardioverter defibrillators or pacemakers. This interactive system has an LCD touch screen with a user-friendly interface that helps clinicians retrieve and study patient information during routine follow-up visits and easily makes programming changes to the implanted devices.

http://youtu.be/dlert3zh8fo

This video demonstrates how an Implantable Cardioverter Defibrillator or ICD is used to treat dangerously fast or irregular heart beats. Run time: 0:58s.

 

Implantable Drug Delivery Systems

More and more advances in modern medicine are relying on electronic devices implanted inside the patient’s body, to minimize the need for regular examinations, surgery, or in-patient time. Nanotechnology allows us to create materials and coatings to construct these devices that are fully biocompatible, so that they integrate seamlessly with the body’s systems.

Implantable drug delivery systems can deliver small amounts of drugs on a regular basis, so that the patient does not need to be injected. Implantable drug delivery systems give a more consistent drug level in the blood compared to injections, which often makes the treatment more effective and reduces side effects.

By using active monitoring capabilities built into the device, the dosage can be adjusted to suit changes in physical activity, temperature changes and other variables.

In treatments such as chemotherapy, which are usually aimed at a specific area of the body, the device can be implanted near the target area, keeping drug concentration much lower in the rest of the body.

Smart implantable insulin pumps are designed so as to offer relief for people with Type I diabetes. These are implantable, active drug delivery devices that build on and go beyond the capabilities offered by passive glucose biosensors.

Regulatory Challenges

Nanomaterials and nanotechnology offer significant promise in the medical device community, as well as many other industry sectors. They also pose a number of regulatory challenges, which as time goes by will become more pressing than the technical challenges. Some of the difficulaties in regulating nanomedical devices are as follows:

  • It is important to determine the intended use of the product, but it can be difficult to define uses among several stakeholders.
  • The indicated patient population must be understood, and there should be clarity about the claimed benefits of a product.
  • Throughout the submission process of products for market approval, it is important to communicate with the FDA or other relevant authority. Manufacturing processes are highly critical for a successful submission. Marketing, sales, labeling and international issues, training and education are all part of this effort.

Conclusions

Nanomedicine will transform healthcare in the coming years, changing the day-to-day business practices of health care organizations and improving how patient care is provided.

Health care organizations must monitor innovations continually, perform clinical trials and developments related to this area and also other evolving health IT solutions.

There is a lot of research going on in this area; however not many products have reached the commercialization stage. There is still a long way to go before all these promising devices become a part of our daily lives.

Sources

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Nanoparticles Enable Earlier Cancer Diagnosis


QDOTS imagesCAKXSY1K 8 From Science Daily, Dec. 17, 2012 — Finding ways to diagnose cancer earlier could greatly improve the chances of survival for many patients. One way to do this is to look for specific proteins secreted by cancer cells, which circulate in the bloodstream. However, the quantity of these biomarkers is so low that detecting them has proven difficult.


 A new technology developed at MIT may help to make biomarker detection much easier. The researchers, led by Sangeeta Bhatia, have developed nanoparticles that can home to a tumor and interact with cancer proteins to produce thousands of biomarkers, which can then be easily detected in the patient’s urine.

This biomarker amplification system could also be used to monitor disease progression and track how tumors respond to treatment, says Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science at MIT.

“There’s a desperate search for biomarkers, for early detection or disease prognosis, or looking at how the body responds to therapy,” says Bhatia, who is also a member of MIT’s David H. Koch Institute for Integrative Cancer Research. She adds that the search has been complicated because genomic studies have revealed that many cancers, such as breast cancer, are actually groups of several diseases with different genetic signatures.

The MIT team, working with researchers from Beth Israel Deaconess Medical Center, described the new technology in a paper appearing in Nature Biotechnology on Dec. 16. Lead author of the paper is Gabriel Kwong, a postdoc in MIT’s Institute for Medical Engineering and Science and the Koch Institute.

Amplifying cancer signals

Cancer cells produce many proteins not found in healthy cells. However, these proteins are often so diluted in the bloodstream that they are nearly impossible to identify. A recent study from Stanford University researchers found that even using the best existing biomarkers for ovarian cancer, and the best technology to detect them, an ovarian tumor would not be found until eight to 10 years after it formed.

“The cell is making biomarkers, but it has limited production capacity,” Bhatia says. “That’s when we had this ‘aha’ moment: What if you could deliver something that could amplify that signal?”

Serendipitously, Bhatia’s lab was already working on nanoparticles that could be put to use detecting cancer biomarkers. Originally intended as imaging agents for tumors, the particles interact with enzymes known as proteases, which cleave proteins into smaller fragments.

Cancer cells often produce large quantities of proteases known as MMPs. These proteases help cancer cells escape their original locations and spread uncontrollably by cutting through proteins of the extracellular matrix, which normally holds cells in place.

The researchers coated their nanoparticles with peptides (short protein fragments) targeted by several of the MMP proteases. The treated nanoparticles accumulate at tumor sites, making their way through the leaky blood vessels that typically surround tumors. There, the proteases cleave hundreds of peptides from the nanoparticles, releasing them into the bloodstream.

The peptides rapidly accumulate in the kidneys and are excreted in the urine, where they can be detected using mass spectrometry.

This new system is an exciting approach to overcoming the problem of biomarker scarcity in the body, says Sanjiv Gambhir, chairman of the Department of Radiology at Stanford University School of Medicine. “Instead of being dependent on the body to naturally shed biomarkers, you’re sampling the site of interest and causing biomarkers that you engineered to be released,” says Gambhir, who was not part of the research team.

Distinctive signatures

To make the biomarker readings as precise as possible, the researchers designed their particles to express 10 different peptides, each of which is cleaved by a different one of the dozens of MMP proteases. Each of these peptides is a different size, making it possible to distinguish them with mass spectrometry. This should allow researchers to identify distinct signatures associated with different types of tumors.

In this study, the researchers tested their nanoparticles’ ability to detect the early stages of colorectal cancer in mice, and to monitor the progression of liver fibrosis.

Liver fibrosis is an accumulation of scarring in response to liver injury or chronic liver disease. Patients with this condition have to be regularly monitored by biopsy, which is expensive and invasive, to make sure they are getting the right treatment. In mice, the researchers found that the nanoparticles could offer much more rapid feedback than biopsies.

They also found that the nanoparticles could accurately reveal the early formation of colorectal tumors. In ongoing studies, the team is studying the particles’ ability to measure tumor response to chemotherapy and to detect metastasis.

The research was funded by the National Institutes of Health and the Kathy and Curt Marble Cancer Research Fund.