pH-responsive drug release and antibacterial activity of chitosan-coated core/shell borate glass-hydroxyapatite microspheres

Multifunctional drug delivery system that can treat bone infection and concurrently accelerate bone tissue regeneration is highly desirable. In this study, we developed a pH-responsive local drug carrier in which a core/shell microsphere consisting of a borate glass core and a mesoporous hydroxyapatite HA shell (BG-HA) was coated with glutaraldehyde-crosslinked chitosan (CS). At neutral pH, a negligible concentration of vancomycin was released from the BG-HA@CS microspheres. However, in an acidic environment, the pores on the HA shell were uncapped due to the swelling of CS, thus accelerating the drug release. The advantage of the BG-HA@CS was evidenced by comparing with HA@CS that was prepared by fully converting borate glass followed by CS coating. The dissolution of the unconverted borate glass core upon immersing in PBS led to an increase in the local pH. This change of pH regulated the swelling/de-swelling behaviours of CS, thereby realizing more sustained drug release. Furthermore, it revealed that the vancomycin-loaded BG-HA@CS provided highly effective antibacterial activity against S. aureus and E. coli , while the vancomycin-loaded HA@CS did not show inhibitory effect on E. coli . The results indicated that the BG-HA@CS would be a promising multifunctional delivery system that can achieve self-regulated drug release, control the acidic environment of bone infection sites and promote bone tissue regeneration.