Cyclodextrin-erythromycin complexes as a drug delivery device for orthopedic application

Abstract

Background

Erythromycin, a hydrophobic antibiotic used to treat infectious diseases, is now gaining attention because of its anti-inflammatory effects and ability to inhibit osteoclasts formation. The aim of this study was to explore a cyclodextrin-erythromycin (CD-EM) complex for sustained treatment of orthopedic inflammation.

Methods and results

Erythromycin was reacted with β-cyclodextrin to form a nonhost-guest CD-EM complex using both kneading and stirring approaches. Physiochemical measurement data indicated that erythromycin and cyclodextrin formed a packing complex driven by intermolecular forces instead of a host-guest structure due to the limited space in the inner cavity of β-cyclodextrin. The CD-EM complex improved the stability of erythromycin in aqueous solution and had a longer duration of bactericidal activity than free erythromycin. Cytotoxicity and cell differentiation were evaluated in both murine MC3T3 preosteoblast cells and RAW 264.7 murine macrophage cells. The CD-EM complex was noncytotoxic and showed significant inhibition of osteoclast formation but had little effect on osteoblast viability and differentiation.

Conclusion

These attributes are especially important for the delivery of an adequate amount of erythromycin to the site of periprosthetic inflammation and reducing local inflammation in a sustained manner.

Keywords:

• erythromycin
• cyclodextrin
• drug stability
• bactericidal activity
• osteoclastogenesis

Acknowledgments

This work was supported by an institutional research grant from Sinai-Grace Hospital, Detroit Medical Center, and the National Natural Science Foundation of China (81071487). We would like to acknowledge Sunxi Wang and Dr Mao for sample characterization.

Disclosure

The authors report no conflicts of interest in this work.