ROS-responsive resveratrol-loaded cyclodextrin nanomicelles reduce inflammatory osteolysis

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pharmacology

Background:

• Inflammatory bone loss results from excessive osteoclast activity, with reactive oxygen species (ROS) contributing to osteoclast differentiation.
• Resveratrol (RSV) scavenges ROS to inhibit osteoclastogenesis, but its therapeutic use is limited by poor solubility and stability.

Purpose of the Study:

• To develop a ROS-responsive nanoplatform for enhanced local delivery of resveratrol.
• To evaluate the efficacy of resveratrol nanomicelles (RSV-NMs) in inhibiting osteoclast formation and preventing bone loss.

Main Methods:

• A PEGylated cyclodextrin (CD)-based nanoplatform was engineered to encapsulate RSV into ROS-responsive nanomicelles (RSV-NMs).
• In vitro studies assessed osteoclast formation, F-actin ring organization, and gene expression of osteoclastic markers.
• In vivo studies evaluated the protective effects against lipopolysaccharide (LPS)-induced bone destruction in a mouse model.

Main Results:

• RSV-NMs exhibited improved solubility, stability, and biocompatibility compared to free RSV.
• In vitro, RSV-NMs significantly inhibited tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cell formation and downregulated key osteoclastic genes (MMP-9, NFATc1, TRAP, cathepsin K).
• In vivo, RSV-NMs reduced osteoclast numbers, increased bone density, and decreased bone resorption area in LPS-treated mice.

Conclusions:

• ROS-responsive RSV-NMs represent a promising strategy for targeted delivery and localized treatment of inflammatory osteolysis.
• The developed nanoplatform effectively mitigates bone loss by inhibiting osteoclastogenesis and scavenging ROS.