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

Abstract

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.