Intra-articular injection of rapamycin microparticles prevent senescence and effectively treat osteoarthritis.
Kaamini M DhanabalanAmeya A DravidSmriti AgarwalRamanath K SharathAshok Kumar PadmanabhanRachit AgarwalPublished in: Bioengineering & translational medicine (2022)
Trauma to the knee joint is associated with significant cartilage degeneration and erosion of subchondral bone, which eventually leads to osteoarthritis (OA), resulting in substantial morbidity and healthcare burden. With no disease-modifying drugs in clinics, the current standard of care focuses on symptomatic relief and viscosupplementation. Modulation of autophagy and targeting senescence pathways are emerging as potential treatment strategies. Rapamycin has shown promise in OA disease amelioration by autophagy upregulation, yet its clinical use is hindered by difficulties in achieving therapeutic concentrations, necessitating multiple weekly injections. Rapamycin-loaded in poly(lactic-co-glycolic acid) microparticles (RMPs) induced autophagy, prevented senescence, and sustained sulphated glycosaminoglycans production in primary human articular chondrocytes from OA patients. RMPs were potent, nontoxic, and exhibited high retention time (up to 35 days) in mice joints. Intra-articular delivery of RMPs effectively mitigated cartilage damage and inflammation in surgery-induced OA when administered as a prophylactic or therapeutic regimen. Together, the study demonstrates the feasibility of using RMPs as a potential clinically translatable therapy to prevent the progression of post-traumatic OA.
Keyphrases
- knee osteoarthritis
- endothelial cells
- oxidative stress
- high glucose
- diabetic rats
- healthcare
- cell death
- dna damage
- signaling pathway
- endoplasmic reticulum stress
- end stage renal disease
- extracellular matrix
- rheumatoid arthritis
- newly diagnosed
- stress induced
- cancer therapy
- palliative care
- ejection fraction
- primary care
- drug delivery
- minimally invasive
- chronic kidney disease
- ultrasound guided
- peritoneal dialysis
- cell proliferation
- pain management
- quality improvement
- coronary artery bypass
- adipose tissue
- risk assessment
- patient reported outcomes
- big data
- machine learning
- coronary artery disease
- skeletal muscle
- acute coronary syndrome
- health information
- social media
- wound healing
- induced pluripotent stem cells