Construction of hyperbranched polyglycerol-based curcumin prodrug via phenol-yne click reaction for pH-responsive and bone-targeted osteoporosis therapy

Abstract

• Construction of hyperbranched polyglycerol-based curcumin prodrug via phenol-yne click reaction. • HPGCA can self-assemble into water dispersible nanoparticles. • HPGCA shows pH-dependent drug release and bone-targeting capability. • HPGCA showed better anti-osteoporosis efficacy than both free Cur and ALN. Osteoporosis is one of the most common chronic metabolic diseases that mainly caused by an imbalance in bone homeostasis. Considered its severe concurrent disorders, osteoporosis has become a global health issue, however, the anti-osteoporosis medications available in clinical practice are confronted with challenges such as high costs, adverse side effects, and limited efficacy. Herein, we reported construction of pH-responsive and bone-targeting nanomedicine (termed HPGCA) via click conjugation of alkyne functionalized hyperbranched polyglycerol (HPG) with curcumin (Cur) and alendronate (ALN) for the first time. We demonstrated that HPGCA exhibit superior water dispersibility, small particle size, and pH-dependent drug release behavior. Results from biological assays indicated that HPGCA displayed desirable bone-targeting capability, strong anti-osteoporosis efficacy, good hemocompatibility, and negligible adverse effects. More importantly, HPGCA showed better anti-osteoporosis efficacy than both free Cur and ALN according results from micro-CT and TRAP staining. The synergistic osteoporosis therapeutic efficacy would be explained by targeting delivering HPGCA to bone tissues and in-situ releasing cargos under acidic environment. Therefore, considered the above aspects, we believe that the innovative nanomedicine is promising for osteoporosis therapy in clinic and will provide new insights for full realization anti-osteoporotic properties of natural compounds.