Bone-Targeting Polymer Vesicles for Effective Therapy of Osteoporosis

With the aging of the population, postmenopausal osteoporosis becomes increasingly widespread and severe as fractures caused by osteoporosis may lead to permanent disabilities and even death. Inspired by extracellular vesicles that participate in bone remodeling, we present a biomimicking polymer vesicle for bone-targeted beta-estradiol (E-2) delivery. This vesicle is self-assembled from a poly(epsilon-caprolactone)(28)-block-poly[(L-glutamic acid)(7)-stat-(L-glutamic acid-alendronic acid)(4)] (PCL28-b-P[Glu(7)-stat-(Glu-ADA)(4)]) diblock copolymer. The alendronic acid (ADA) on the coronas endows the polymer vesicles with a high bone affinity and acts synergistically with E-2 to achieve an enhanced therapeutic effect. As confirmed with ovariectomized osteoporosis rat models, bone loss was significantly reversed as the recovery rates of total BMD (bone mineral density) and trabecular BMD were 70.4% and 99.3%, respectively. Overall, this work provides fresh insight into the treatment of osteoporosis.