Enhanced effects of osteoclastogenesis inhibition by curcumin-delivering heparin nanoparticles

Abstract

Curcumin has various pharmacological activities such as anti-inflammatory, antioxidant, antimicrobial and antitumor activity. However, its use has been limited due to its poor solubility in water and minimal systemic bioavailability. Thus, we developed curcumin-delivering heparin-based nanoparticles and evaluated the inhibition effects of osteoclastogenesis by curcumin-delivering heparin nanoparticles (Cur-HD NPs). Cur-HD NPs were dispersed well in aqueous solution by forming self-assembled nanoparticles and showed sustained release of curcumin. In vitro studies, HD NPs facilitated intracellular delivery of curcumin into macrophages and osteoclasts, and thus, Cur-HD NPs effectively inhibited osteoclastogenesis in a dose-dependent manner by suppressing tartrate-resistant acid phosphatase (TRAP) activity and TRAP-positive multinucleated cells as well as by reducing the expression of osteoclast marker genes (i.e., TRAP and nuclear factor of activated T cells cytoplasmic 1 (NFATc1)). Furthermore, Cur-HD NPs markedly stimulated apoptosis of osteoclasts. Therefore, we hope that Cur-HD NPs will be useful nanodrugs for the treatment of bone-related diseases.