Amelioration of Post-traumatic Osteoarthritis by Iontophoretic Liposomal Strontium Ranelate Collaborated with Low-Intensity Pulsed Ultrasound in Rats

Osteoarthritis (OA), the most common form of arthritis, affects the whole synovial joint. Post-traumatic osteoarthritis (PTOA) is an important subtype of OA which develops after joint injury. The anti-PTOA effects of iontophoretic liposome-encapsulated strontium ranelate (L-SR) combined with low-intensity pulsed ultrasound (LIPUS) were examined by a culture of human OA chondrocytes (HOACs) in alginate beads and verified on an anterior cruciate ligament transection PTOA rat model. The aim of this study is to evaluate and establish an anti-PTOA therapy combined with L-SR, transdermal iontophoresis, and LIPUS. Treatment with 10^-4 M L-SR with LIPUS-enhanced type II collagen and glycosaminoglycans (GAGs) as L-SR with LIPUS reduced the MMP-13, IL-1β, and TNF-α in HOACs. Iontophoretic L-SR at 15 mg with LIPUS increased the weight bearing, exercise endurance, GAG density, and type II collagen intensity, while L-SR with or without LIPUS further decreased MMP13 and proinflammatory cytokines in vivo. The RBC, WBC, and serum biochemistry values were not significantly affected by the treatments. Liposome encapsulation and iontophoresis reinforce the anti-PTOA effects of SR and the addictive LIPUS further improves weight-bearing and endurance performance in the rats with PTOA. Thus, iontophoretic L-SR with LIPUS could be a potential therapy for PTOA.