In Situ Self-Assembling Micellar Depots that Can Actively Trap and Passively Release NO with Long-Lasting Activity to Reverse Osteoporosis

Treatment with exogenous nitric oxide (NO) donors is regarded as being effective against osteoporosis. However, NO has a short half-life, limiting its clinical usefulness. To overcome this limitation, an injectable microparticle (MP) system is developed that consists of phase-change materials capric acid (CA) and octadecane, and encapsulates a NO donor. The therapeutic efficacy of the MPs is evaluated in ovariectomized (OVX) rats with osteoporosis. Upon subcutaneous administration, the MPs undergo a phase transition, leaching out the NO donor and generating NO bubbles that are instantly covered by a layer of tightly packed CA surfactant molecules, forming micellar depots. The in situ self-assembling micellar depots can actively protect the NO bubbles, prolonging their half-life, while the entrapped NO may passively diffuse through the micellar depots over time, performing a long-lasting therapeutic function, reversing the OVX-induced osteoporosis. It is possible to use the concept of in situ self-assembling micellar depots developed herein to expand the therapeutic effect of NO in its diverse range of clinical applications.