A single intraarticular injection of nanotechnology-based drug formulation as a safe osteoarthritis disease- modifying drug.

Title : A single intraarticular injection of nanotechnology-based drug formulation as a safe osteoarthritis disease- modifying drug.

Abstract:

Osteoarthritis (OA) is a leading cause of chronic pain and disability, affecting >500 million adults globally. Clinically
accepted treatment strategies are often ineffective, and opioids have been traditionally recommended as options for OA pain, contributing to a social problem – the opioid crisis. The expression level of vascular endothelial growth factor (VEGF) is highly connected with OA severity1-4. Recently, we identified distinct roles for VEGF receptors: VEGFR1 is primarily responsible for joint pain transmission, and VEGFR2 is for cartilage degeneration5,6. Intraarticular (IA) injection (twice/week) of pazopanib, an FDA-approved selective inhibitor of VEGFR1/VEGFR2, markedly reduced joint pain and inhibited cartilage degeneration. To facilitate IA treatment of pazopanib in clinical settings, we developed a nanotechnology-based drug formulation for prolonged and sustained drug efficacy (referred to as nano-PAZ). We validated the drug efficacy of a single IA injection of nano-PAZ in two different OA models in different species (mice, rats) for reduced pain and pathology at different stages of OA disease progression (inflammatory, early- and, advanced OA). Toxicologic evaluations were done for safety using In Vivo Imaging analyses and drug abuse liability tests to ensure no addiction properties. A single IA injection of nano-PAZ abolished joint pain for >16 weeks in our preclinical animal models, in part, via reduction of (i) nerve growth factor (NGF) and its cognate receptor TrkA in the synovium and dorsal root ganglion (DRG) sensory neurons; (ii) NFkappaB and spinal glial activity. In conclusion, a single IA injection of nano-PAZ rapidly reduces knee joint pain and protects cartilage at any stage of OA disease progression, suggesting its potential as a novel OA disease-modifying drug. Nano-PAZ could be rapidly translatable to clinical settings not only for knee OA but also for a broad spectrum of musculoskeletal pain, including low back pain.

Biography:

Dr. Im Sampen is a Principal Investigator funded by NIH, the Department of Defense (DoD), Veterans Affairs (VA) and Foundations as a multidisciplinary osteoarthritis (OA) pain research group. Her research has been instrumental in establishing preclinical rodent models to examine mutual cause-and-effect relationships in OA that link tissue degeneration with pain. She has served on multiple NIH and Foundation study sections administered by NIAMS, VA, or international funding agencies. She also served as an Editor-In-Chief for Gene Reports or Executive Editor (Gene) and an Editorial board member of numerous international journals. She has been a member of the Orthopaedic Research Society (ORS) since 2000 and served the ORS as Nominating Committee (elected), an Executive Member of Women’s Leadership Forum and Asian Leadership Forum member. She received various awards and honors, such as the Arthritis National Research Foundation Scholar Award, OARSI Investigator Award, Kappa Delta Elizabeth Winston Lanier Award from the ORS, and VA Research Scientist Award.Dr. Im Sampen is a Principal Investigator funded by NIH, the Department of Defense (DoD), Veterans Affairs (VA) and Foundations as a multidisciplinary osteoarthritis (OA) pain research group. Her research has been instrumental in establishing preclinical rodent models to examine mutual cause-and-effect relationships in OA that link tissue degeneration with pain. She has served on multiple NIH and Foundation study sections administered by NIAMS, VA, or international funding agencies. She also served as an Editor-In-Chief for Gene Reports or Executive Editor (Gene) and an Editorial board member of numerous international journals. She has been a member of the Orthopaedic Research Society (ORS) since 2000 and served the ORS as Nominating Committee (elected), an Executive Member of Women’s Leadership Forum and Asian Leadership Forum member. She received various awards and honors, such as the Arthritis National Research Foundation Scholar Award, OARSI Investigator Award, Kappa Delta Elizabeth Winston Lanier Award from the ORS, and VA Research Scientist Award.