Chlorhexidine-Loaded Amorphous Calcium Phosphate Nanoparticles for Inhibiting Degradation and Inducing Mineralization of Type I Collagen.

A major shortcoming of contemporary dentin adhesives is their limited durability. Exposed collagen fibrils within the bonding interface are degraded by matrix metalloproteinases (MMPs), resulting in aging of the resin-dentin bond. In this study, chlorhexidine-loaded amorphous calcium phosphate (ACP) nanoparticles were synthesized to induce the mineralization of collagen fibrils. The nanoparticles sustainably released chlorhexidine to inhibit MMPs during mineralization. Three types of ACP nanoparticles were prepared: N-ACP containing no chlorhexidine, C-ACP containing chlorhexidine acetate, and G-ACP containing chlorhexidine gluconate, which had a higher drug-loading than C-ACP. Scanning and transmission electron microscopy indicated that the synthesized nanoparticles had diameters of less than 100 nm. Some had diameters of less than 40 nm, which was smaller than the width of gap zones in the collagen fibrils. Energy dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy, and high performance liquid chromatography confirmed the presence of chlorhexidine in the nanoparticles. X-ray diffraction confirmed that the nanoparticles were amorphous. The drug loading was 0.11% for C-ACP and 0.53% for G-ACP. In vitro release profiles indicated that chlorhexidine was released sustainably via first-order kinetics. Released chlorhexidine inhibited the degradation of collagen in human dentine powder, and its effect lasted longer than that of pure chlorhexidine of the same concentration. The ACP could induce the mineralization of self-assembled type I collagen fibrils. The chlorhexidine-loaded ACP nanoparticles sustainably released chlorhexidine and ACP under appropriate conditions. This is useful for inhibiting degradation and inducing the mineralization of dentine collagen fibrils.