NEW DRUG DELIVERY CAPSULE MAY REPLACE INJECTIONS

Given a choice, most patients would prefer to take a drug orally instead of getting an injection. Unfortunately, many drugs, especially those made from large proteins, cannot be given as a pill because they get broken down in the stomach before they can be absorbed.

To help overcome that obstacle, researchers at MIT and Massachusetts General Hospital (MGH) have devised a novel drug capsule coated with tiny needles that can inject drugs directly into the lining of the stomach after the capsule is swallowed. In animal studies, the team found that the capsule delivered insulin more efficiently than injection under the skin, and there were no harmful side effects as the capsule passed through the digestive system.

"This could be a way that the patient can circumvent the need to have an infusion or subcutaneous administration of a drug," says Giovanni Traverso, a research fellow at MIT's Koch Institute for Integrative Cancer Research, a gastroenterologist at MGH, and one of the lead authors of the paper, which appears in the Journal of Pharmaceutical Sciences.

Although the researchers tested their capsule with insulin, they anticipate that it would be most useful for delivering biopharmaceuticals such as antibodies, which are used to treat cancer and autoimmune disorders like arthritis and Crohn's disease. This class of drugs, known as "biologics," also includes vaccines, recombinant DNA, and RNA.

"The large size of these biologic drugs makes them nonabsorbable. And before they even would be absorbed, they're degraded in your GI tract by acids and enzymes that just eat up the molecules and make them inactive," says Carl Schoellhammer, a graduate student in chemical engineering and a lead author of the paper.

Safe and effective delivery

Scientists have tried designing microparticles and nanoparticles that can deliver biologics, but such particles are expensive to produce and require a new version to be engineered for each drug.

Schoellhammer, Traverso, and their colleagues set out to design a capsule that would serve as a platform for the delivery of a wide range of therapeutics, prevent degradation of the drugs, and inject the payload directly into the lining of the GI tract. Their prototype acrylic capsule, 2 centimeters long and 1 centimeter in diameter, includes a reservoir for the drug and is coated with hollow, stainless steel needles about 5 millimeters long.

Previous studies of accidental ingestion of sharp objects in human patients have suggested that it could be safe to swallow a capsule coated with short needles. Because there are no pain receptors in the GI tract, patients would not feel any pain from the drug injection.

To test whether this type of capsule could allow safe and effective drug delivery, the researchers tested it in pigs, with insulin as the drug payload. It took more than a week for the capsules to move through the entire digestive tract, and the researchers found no traces of tissue damage, supporting the potential safety of this novel approach.

They also found that the microneedles successfully injected insulin into the lining of the stomach, small intestine, and colon, causing the animals' blood glucose levels to drop. This reduction in blood glucose was faster and larger than the drop seen when the same amount of glucose was given by subcutaneous injection.

"The kinetics are much better, and much faster-onset, than those seen with traditional under-the-skin administration," Traverso says. "For molecules that are particularly difficult to absorb, this would be a way of actually administering them at much higher efficiency."

"This is a very interesting approach," says Samir Mitragotri, a professor of chemical engineering at the University of California at Santa Barbara who was not involved in the research. "Oral delivery of drugs is a major challenge, especially for protein drugs. There is tremendous motivation on various fronts for finding other ways to deliver drugs without using the standard needle and syringe."

Further optimization

This approach could also be used to administer vaccines that normally have to be injected, the researchers say.

The team now plans to modify the capsule so that peristalsis, or contractions of the digestive tract, would slowly squeeze the drug out of the capsule as it travels through the tract. They are also working on capsules with needles made of degradable polymers and sugar that would break off and become embedded in the gut lining, where they would slowly disintegrate and release the drug. This would further minimize any safety concern.

Epidural Steroid Injections For Neuropathy Warning! Vid

The problem with neuropathy is that it's one of those diseases which is impossible to cure and difficult to treat. This leaves the door open for desperate patients to try anything they may have seen advertised, or have heard about from friends. One of the current 'treatments' gaining popularity among neuropathy patients is the epidural steroid injection, despite the fact that it is being promoted as a treatment for severe back pain and not for the most common symptoms of neuropathy. Some people with neuropathy caused by impacted nerves or injury may benefit under controlled and expert conditions but it's dangerous to assume that it's beneficial for all forms of nerve damage. Today's Dr Oz clip warns about the dangers of these injections despite their being the number one treatment for lower back pain. They are not FDA approved and you should never go ahead with this sort of treatment if you have neuropathy and have not made the decision with the full agreement of a neurologist. The trouble is that people will clutch at straws when their symptoms are so severe. They will grab at a headline, read half a story and assume that such a treatment will be good for them. It's even more dangerous if unscrupulous clinics and doctors also misinform their patients in the search for easy earnings (as shown in the video). Forewarned is forearmed they say.



Epidural Steroid Injections, The Truth... Finally! / Part 1

The TRUTH about Epidural Injections. "If any good can come from this, in addition to shining a light on the need for greater oversight of compounding pharmacies, it might be that the media attention on steroid injections will allow patients to become better-informed consumers. For patients, it is buyer beware." Dr. Ray M. Baker, Anesthesiologist and President of the International Spine Intervention Society.

 

https://www.youtube.com/watch?v=QCbzXqrG0ic

Neuropathic Pain Relief With PAP Injections

This fascinating article from sciencedaily.com (see link below) looks at the potential of  so-called PAP injections to relieve pain. You'll need to read it to find out what that is.  Many people try acupuncture in a bid  to help reduce their neuropathy symptoms. Some achieve some success and others none at all. The fact that acupuncture body maps are being studied by the University of North Carolina, with a view to injecting a protein at those points to achieve long-lasting pain relief, is very interesting, especially for those who have long had faith in aspects of ancient Chinese medicine.
 Neuropathy is that sort of disease and people respond differently to every form of medication or treatment, which of course makes it very difficult indeed to treat. Those who suffer from a lot of pain and may be on or approaching morphine treatment, may well find this article very interesting for the future. You may not understand everything here but you'll get the general idea.

Pain Relief With PAP Injections May Last 100 Times Longer Than a Traditional Acupuncture Treatment

ScienceDaily (Apr. 23, 2012)

Scientists at the University of North Carolina at Chapel Hill have identified a new way to deliver long-lasting pain relief through an ancient medical practice.

In an article published in the April 23 online edition of Molecular Pain, UNC researchers describe how exploiting the molecular mechanism behind acupuncture resulted in six-day pain relief in animal models. They call this new therapeutic approach PAPupuncture.

Principal investigator Mark J. Zylka, PhD, associate professor in the Department of Cell and Molecular Physiology and the UNC Neuroscience Center, said this is a promising study that moves his lab's work with prostatic acid phosphatase, known as PAP, towards translational research.

Several years ago, Zylka and members of his lab documented how injecting PAP into the spine eased chronic pain for up to three days in rodents. The only problem was PAP's delivery.

"Spinal injections are invasive and must be performed in a clinical setting, and hence are typically reserved for patients with excruciating pain," said Zylka. Though he had never received acupuncture or researched traditional Chinese medicine, Zylka said recent research showing how acupuncture relieved pain caught his eye.

"When an acupuncture needle is inserted into an acupuncture point and stimulated, nucleotides are released. These nucleotides are then converted into adenosine," said Zylka. Adenosine has antinociceptive properties, meaning adenosine can decrease the body's sensitivity to pain. The release of adenosine offers pain relief, but for most acupuncture patients that relief typically lasts for a few hours.

"We knew that PAP makes adenosine and lasts for days following spinal injection, so we wondered what would happen if we injected PAP into an acupuncture point?" Zylka said. "Can we mimic the pain relief that occurs with acupuncture, but have it last longer?"

To find out, Zylka and his lab injected PAP into the popliteal fossa, the soft tissue area behind the knee. This also happens to be the location of the Weizhong acupuncture point. Remarkably, they saw that pain relief lasted 100 times longer than a traditional acupuncture treatment. What's more, by avoiding the spine the researchers could increase the dose of PAP. A single injection was also effective at reducing symptoms associated with inflammatory pain and neuropathic pain.

"Pinning down the mechanisms behind acupuncture, at least in animal models, was critical," said Zylka. "Once you know what chemicals are involved, you can exploit the mechanism, as we did in our study."

The next step for PAP will be refining the protein for use in human trials. UNC has licensed the use of PAP for pain treatment to Aerial BioPharma, a Morrisville, N.C.-based biopharmaceutical company.

Zylka said PAP could be applicable to any area where regional anesthesia is performed to treat pain. And PAP has the potential to last longer than a single injection of local anesthetic -- the class of drugs used in regional anesthesia.
"When it comes to pain management, there is a clear need for new approaches that last for longer periods of time," said Julie Hurt, PhD, a postdoctoral fellow in Zylka's lab.

Zylka co-authored the paper with Hurt. The research was undertaken at UNC and was supported by the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health.
http://www.sciencedaily.com/releases/2012/04/120423103715.htm