Local administration and enhanced release of bone metabolic antibodies from hydroxyapatite/chondroitin sulfate nanocomposite microparticles using zinc cations

Abstract

As a local delivery carrier of bone metabolic proteins, we have previously reported hydroxyapatite/chondroitin sulfate composite microparticles (HAp/ChS) and their formulation method using zinc cations (Zn), and the in vitro release properties of proteins from the microparticles. Herein, we report the release properties of model antibodies such as immunoglobulin (IgG), human IgG (hIgG), and denosumab (Dmab) from HAp/ChS using this formulation method. Adding Zn in the formulation of IgG loaded with HAp/ChS microparticles enhanced the release of antibodies from HAp/ChS in phosphate buffer saline. In addition, the biological activity of Dmab released from HAp/ChS formulated with Zn was significantly higher than that without Zn. These results suggest a possible beneficial effect on the treatment for local bone diseases. The sclerostin monoclonal antibody (Sclmab) promotes fracture healing. We prepared HAp/ChS microparticles loaded with Sclmab and locally administered the microparticles into a drilled hole in the distal femoral bone of young rats. After three weeks, the area of the newly formed osteoid around the drilled hole where HAp/ChS loaded with Sclmab and Zn was locally administered was significantly higher than that observed in the control group (normal saline). Thus, HAp/ChS microparticles and the formulation method of monoclonal antibodies using Zn could be useful in the treatment of local bone diseases.