Project 465117

Osteoarthritis (OA) is one of the most common joint diseases in the world, affecting more than 6 million Canadians and costing $11 billion to the Canadian health care system in 2016. People affected by the disease mainly use analgesics and anti-inflammatory drugs to relieve their symptoms, and as a last resort arthroplasty. To date, there is no curative pharmacological treatment for osteoarthritis. Our laboratory has shown the effectiveness of a treatment based on the synergistic action of antagonistic peptides of the ETA receptors of endothelin and BKB1 of bradykinin, to reduce the progression of disease and joint pain in an animal model of OA. Nevertheless, the avascular nature of cartilage is responsible for the poor control of drug distribution in it. Water-rich nanogels enable effective targeting and delivery of drugs, reducing both rapid elimination of drugs in the joint and side effects, as well as improving patient compliance to its treatment. Thus, our main objective is to develop biopolymeric nanogels (NG) biocompatible and biodegradable for the local administration of these peptides in order to increase their effectiveness for the treatment of OA. We will first synthesize and characterize peptidic nanogels from natural biomaterials. NG's affinity for cartilage will enable effective targeting in it. We will then determine their biocompatibility in human cartilage cells and in animals to ensure their safety. Finally, we will evaluate their distribution in the body and their effectiveness for the long-term treatment of osteoarthritis in an animal model of OA.This approach aims to develop an innovative delivery system that overcomes the obstacles related to the delivery of therapeutic molecules into non-vascularized cartilage. This new approach for the treatment of osteoarthritis will be useful early in the disease process, and could prevent loss of cartilage, inflammation and pain, and finally to promote joint cartilage restoration.