Abstract
As the elderly population grows, the prevalence of osteoporosis is increasing. Osteoporosis is a systemic skeleton disease which happens on elder people and menopausal women because of bone loss. As the microstructure of bone tissue weakened, it will possibly cause bone fracture, which causes pain, disability, inconvenience, and even indirectly lead to death. Under normal physiological conditions, osteoblasts are responsible for bone formation and osteoclasts remove the old bones, which is a continuous process called bone remodeling. Osteoporosis occurs when bone resorption rate is faster than bone formation rate. Therefore, it is critical to strike a balance between bone resorption and bone formation rate in osteoporosis treatments. Nitric oxide is an endogenous gas molecule, which is reportedly able to modulate bone resorption and formation. Previous animal and human studies demonstrate that nitric oxide has the potential to reverse the estrogen deficiency-induced bone loss. However, due to the short half-life of nitric oxide, the frequency of its administration need to be increased, restricting the application of nitric oxide on osteoporosis treatment. Our study developed a temperature-sensitive composite delivery system, which is comprised of capric acid and octadecane, to carry a nitric oxide donor(DETA-NONOate) for treating osteoporosis. At body temperature, the capric acid/octadecane carrier system undergoes phase transition from solid to liquid, causing the release of DETA-NONOate. DETA-NONOate reacts with proton generated by capric acid and forms nitric oxide bubbles, which further regulate the balance between osteoblast and osteoclast. Meanwhile, capric acid, a surfactant molecule, stabilizes the structure of the generated nitric oxide bubbles and prolongs their half-life. On the other hand, capric acid is able to suppress the differentiation of osteoclasts. Accordingly, this carrier system has the biphasic effects of promoting the function of bone-forming osteoblasts and inhibiting the function of bone-resorbing osteoclasts in vitro. In vivo study, this carrier system not only largely decreases frequency of drug application but also successfully alleviates osteoporosis in vivo.