Sustained release intra-articular medication could revolutionize the treatment of osteoarthritis in horses, with a single injection lasting for months and having no adverse side effects on other organs.
Ontario Veterinary College researcher Mark Hurtig and his team are embarking on this new technology, which could revolutionize joint treatments and much more.
Sustained release formulations could have great potential in delivering antibiotics, parasiticides or other drugs that require long treatment regimes or treatment of tissues that are difficult to penetrate with oral or other injectable drugs. There could be applications for direct injection of drugs into joints, the spinal column, tendon sheaths and even eyes.
Hurtig’s current research project on sustained release using intra-articular medication began in the Spring of 2016 with objectives of slowing down the progression and signs of joint disease. Currently there are no drugs registered for use in the treatment of equine osteoarthritis, partly because there are challenges with conventional drugs reaching joint tissues in adequate concentrations. A good example is glucosamine which has minimal absorption by the equine gastrointestinal tract. Describing the intra-articular medication in development, Hurtig says: “We can treat a single or multiple joints without having to poison the whole horse.”
How does it work?
“Sustained release technology targets the joint space and the joint space alone,” says Hurtig. “The drug levels in the rest of the body are miniscule.”
With low systemic exposure, this means there should be no problems with ulcers, renal disease and other complications that can result from NSAIDS. Sustained release technology is about binding the drug to a carrier and having that carrier break down slowly to release the active pharmacological ingredient (API).
In this case a liquid polymer mixture becomes a semi-solid gel after it is injected into the joint. The gel is broken down slowly releasing the API which can be a drug, therapeutic protein or growth factor. The polymer mixture is described by Hurtig as ‘comprised of garden variety molecules’ which are readily available, inexpensive and well accepted as safe in food and drug manufacturing.
A little does a lot
Dr Hurtig’s team has shown that as little as 200mg of drug (a small fraction of one oral dose) could last three to four months or longer. In many cases this means using two to three orders of magnitude less drug.
“It is a really local therapy and a very green technology,” explains Hurtig. “With less drugs being excreted out into the environment, this means less impact on soil and drinking water.”
Fewer drugs could prove better for the horse, environment and pocketbook.
Traditional treatment of osteoarthritis
Conventional treatments manage the pain and inflammation in joint disease. There are no treatments registered for treating equine osteoarthritis though injectable corticosteroids, hyaluronic acid, platelet rich plasma, IRAP (interleukin receptor antagonist protein), NSAIDs and nutraceuticals help control the symptoms. These treatments can suppress inflammation but have no proven effect on repairing cartilage.
In some cases, such as prolonged use of long-acting corticosteroids, there is a negative metabolic effect on articular cartilage and can promote additional joint degeneration. Hyaluronic acid, platelet rich plasma, and many of the new biologic therapies have a relatively short acting effect of weeks to a few months.
Prolonging the effect of such treatments with sustained release carriers could be one answer to practical cost-effective management of joint disease. Drugs that are too expensive or toxic to administer to horses by other routes could be delivered by direct injection.
In collaboration with Dr Beth Gillies at the University of Western Ontario, Hurtig’s team has been developing carrier/drug prototypes for preliminary trials in horses.
Funding for this research has been provided by Equine Guelph.