Our agent is in the rear of the prosthetic joint
Orthopedic surgeons really need such a contrast agent!
Nanonewsnet based on Hospital for Special Surgery materials:
Researchers Identify Tool to Detect Total Joint Replacement Surgeries that are Starting to Fail
A recent study conducted by American scientists has shown that doctors will soon be able to get an effective tool for detecting the loosening of the prosthesis after endoprosthesis surgery. Loosening of prostheses is the most common reason for the unsuccessful outcome of such operations. The work demonstrates that a small molecule supplemented with new properties can be used to identify patients at risk and to deliver drugs that can stop this process.
"This method can be used to visualize the inflammation around the implant, which will warn the surgeon about the possible risk of loosening the prosthesis. The system can also be used to deliver medications that can block inflammation, which is the cause of loosening," says Steven Goldring, MD, chief researcher at Hospital for Special Surgery (HSS), who participated in the study.
This work is the result of collaboration between HSS scientists and the University of Nebraska Medical Center (University of Nebraska) – published online in the journal Molecular Pharmaceuticals (Ke Ren et al., Early Detection and Treatment of Wear Particle-Induced Inflammation and Bone Loss in a Mouse Calvarian Osteolysis Model Using HPMA Copolymer Conjugates).
Every year, 1.5 million joint replacement surgeries, such as hip and knee, are performed in the world. Over the next 10 years, 10 percent of patients who have undergone endoprosthetics need a repeat operation, which is not always successful. For example, up to 20 percent of patients who have undergone repeated knee replacement may experience pain for several months or even years after surgery.
The most common reason for the unsuccessful outcome of such operations is the loosening of the prosthesis that occurs over time. "Loosening can be caused by the destruction of the materials from which the prosthesis is made, leading to the formation of "wear products" released into the tissues surrounding the prosthesis," explains Dr. Gouldring. "These particles cause severe inflammation and accumulate between the bone and the prosthesis. Local inflammation destroys the bone, and the prosthesis is loosened."
In medicine, this process is known as osteolysis. "Osteolysis is the most frequent long–term complication of endoprosthetics, and it is he who causes repeated operations associated with even greater complications and significant financial costs," says Ed Purdue, PhD, director of the HSS Osteolysis Laboratory. "There are no real methods of osteolysis therapy other than repeated surgery, and this disease is very difficult to track."
Although imaging tools such as X-rays, computed tomography and magnetic resonance imaging determine bone damage and loosening of the prosthesis, doctors ideally would really like to have a tool that allows them to identify the early roots of the problem when inflammation is just beginning and the bone has not yet been destroyed.
"When patients feel pain and clear radiographic evidence is obtained, unfortunately, significant bone loss has already occurred, which cannot be easily restored," says Dong Wang, associate professor of the Department of Pharmaceutical Sciences at the University of Nebraska Medical Center.
A few years ago, Dr. Wang developed a nanocomplex that contained a powerful anti-inflammatory drug. The nanocarrier he used in this development was used in the past to deliver chemotherapeutic drugs to cancer cells. This system chooses cancer cells as its targets, focusing on the abnormal growth of blood vessels involved in carcinogenesis. Scientists were interested in whether it could be used to detect abnormal growth of blood vessels and inflammation in other diseases and, possibly, to deliver medicines. In 2006, they demonstrated that the system could potentially be used to target arthritic joints. In a new study, the ability of this tool to detect the loosening of prostheses was tested.
Carrying out endoprosthetics on mice would be too complicated a procedure, therefore, in order to simulate what happens when a joint replacement fails in humans, scientists resorted to a simplified version. They injected particles of the prosthesis material, formed as a result of its wear, into the soft tissues above the skull of mice. This caused an inflammatory reaction similar to that observed in humans. Then they injected nanocarriers labeled with a near-infrared fluorescent marker into the blood of animals and showed that they tend to inflamed cells. The autopsy confirmed these results. In addition, the nanosystem was able to deliver the anti-inflammatory drug dexamethasone directly to the area of inflammation, where it successfully suppressed it and prevented osteolysis.
To diagnose inflammation caused by particles of the wearable prosthesis material, scientists have developed a contrast agent (P-IRDye) for optical imaging, fluorescing in the near-infrared light range, based on a copolymer (N-(2-hydroxypropyl)methacrylamide) (N-(2-hydroxypropyl)methacrylamide, HPMA). 6 days after the introduction of P-IRDye into the vein of the tail of mice, fluorescent dye accumulated in the area of inflammation in the soft tissues above the skull of the animals (pictured).
In the control group, P-IRDye was administered to animals without inflammation induced by wear particles and was evenly distributed throughout the body.
"One of the problems of systemic drug delivery is that they affect the normal tissues of the whole body, causing side effects," explains Dr. Gouldring. "With these nanoparticles, systemic toxicity can be avoided and drugs can be selectively delivered to the site of inflammation."
Dr. Purdue notes that, most likely, doctors will eventually use other medicinal substances rather than dexamethasone for the treatment of osteolysis, but the article provides proof of the validity of the concept itself.
The nanocarrier system should be tested on animal models with prosthetic joints, and then in clinical trials, but its developers believe that they will be able to quickly move from proof of principle to research on the human body.
"One of the advantages here is that phases I and II of clinical trials of this system have already been approved in Europe and the USA to improve cancer chemotherapy, so we have already overcome one of the regulatory barriers," explains Dr. Gouldring. "What we are now doing is searching for other therapeutic agents that could be combined with nanocarriers for more selective targeting of the inflammatory process caused by the wear particles of the prosthesis.
Portal "Eternal youth" http://vechnayamolodost.ru29.04.2011