Scientists at the Massachusetts Institute of Technology (MIT) have developed a nanotechnology solution that may help in the management of osteoarthritis in patients.
Osteoarthritis is a painful condition that affects mostly older adults, with women being the more susceptible. It affects mostly the softer, cartilaginous joints of the human body.
Usually, the condition starts with an infarction to a joint. This could also be caused by a disease to a joint or as a result of wear and tear as a result of use over the years.
At present, there is treatment or way to stop this condition from progressing. The only methods currently employed in its management, involves the use of pain reliefs in relieving the pain associated with the condition.
Ostearthritis is becoming an even greater problem with a rising aging population, having a much higher average body weight — both risk factors for the condition.
Furthermore, because pain is the predominant symptom, osteoarthritis is contributing to the opioid addiction crisis. Finding innovative ways to interject in this disease’s onward march is more pressing than ever.
Interestingly, a new approach to dealing with osteoarthritis involving an innovative nano-technological approach could offer succor to sufferers of this condition.
The procedure involves sending therapeutic agents deeper into the affected cartilage and keeping them active for a long period of time.
Solving The Problem By Improving Drug Delivery To Joints
So far, no chemical agents tested by scientists have shown valuable results in human patients unlike in animal models. However, the authors of this new study believe that “[m]any of these shortcomings are rooted in inadequate drug delivery.”
This is for two main reasons. Firstly, the joints have a lack of blood supply, meaning that specialists must inject drugs directly into the joints themselves. Secondly, lymphatic drainage tends to rapidly remove compounds injected into joints.
To overcome this hurdle, the scientists focused on designing a way to deliver and keep drugs in the joint for a longer time while also diving deeper into cartilage, thereby taking medication directly to the cells where it is needed.
The medication they focused on was insulin-like growth factor 1 (IGF-1), a compound that has shown promise in some clinical trials. This growth factor promotes growth and survival of chondrocytes, which are the cells that make up healthy cartilage.
Utilizing Tiny (Nanoscale) Spherical Molecules
The researchers designed a nanoscale spherical molecule as a carrier for IGF-1. The molecule is composed of many branches, called dendrimers, that emanate from a central core.
Each branch ends with a positively charged region that is attracted to the negative charge on the surface of chondrocytes.
The molecules also include a swinging polymer arm that covers up and intermittently neutralizes the positive charges. The researchers attached IGF-1 molecules to the surface of this sphere and injected the compound into the joints of rats.
Once these particles are in the body, they bind to cartilage and lymphatic drainage cannot remove them. From there, they can begin to diffuse into the tissue.
However, the spheres do not bond permanently, as this would keep them locked to the surface of the cartilage. The flexible polymer arm occasionally covers the charges, allowing the molecule to move and submerge itself deeper into the tissue.
“We found an optimal charge range so that the material can both bind the tissue and unbind for further diffusion, and not be so strong that it just gets stuck at the surface.” – Lead study author Brett Geiger, an MIT graduate student
As IGF-1 is introduced to the chondrocytes, it induces the release of proteoglycans, or the raw material of cartilage. IGF-1 also encourages cellular growth and reduces the rate of cell death.
Extending the Therapeutic Window
In an effort to extend the therapeutic window, the researchers injected this hybrid molecule into rats’ joints. It had a half-life of 4 days (the time it takes for the drug to reduce to half its initial volume), which is around 10 times longer than when scientists inject IGF-1 alone. Importantly, its therapeutic effect lasted for 30 days.
Compared with rats that did not receive the drug, those that did saw reduced joint damage. Also, there was a significant reduction in inflammation.
Of course, rat cartilage is much thinner than that of humans; theirs is around 100 micrometers thick, whereas a human’s is closer to 1 millimeter.
In a separate experiment, the scientists proved that these molecules were able to penetrate to a thickness that would be relevant for a human patient.
This is just the first phase of research investigating the use of these molecules to deliver drugs into cartilage. The team plans to continue along the same lines and study other chemicals, including drugs that block inflammatory cytokines and nucleic acids including DNA and RNA.
The study appears alongside an editorial on the use of nanotechnology in osteoarthritis research.
The author, Christopher H. Evans, said:
“These are highly encouraging data. […] [T]here is no other drug delivery system that can influence the metabolism of chondrocytes in situ throughout the full thickness of articular cartilage in a sustained fashion.”
Though the new method is in its infancy, this approach might eventually mean that doctors could significantly slow the course of osteoarthritis with biweekly or monthly injections.
Source: Medical News Today