Environmental pH-controlled loading and release of protein on mesoporous hydroxyapatite nanoparticles for bone tissue engineering.

To explore the controlled delivery of protein drugs in micro-environment established by osteoblasts or osteoclasts, the loading/release properties of bovine serum albumin (BSA) depending on pH environment were assessed. The adsorption amounts over mesoporous hydroxyapatite (MHA) or hydroxyapatite (HA) decreased as the pH increased, negatively correlating with zeta-potential values. The adsorption behavior over MHA fits well with the Freundlich and Langmuir models at different pHs. The results suggest that the adsorbed amount of protein on MHA or HA depended on the pH of protein solution. MHA adsorbed BSA at basic pH (MHApH 8.4) exhibited a different release kinetics compared with those in acid and neutral environments (MHApH 4.7 and MHApH 7.4), indicating that the release of protein could be regulated by environmental pH at which MHAs adsorb protein. MHApH 8.4 showed a sustained release for 6h before a gradual release when immersing in acidic environment, which is 2h longer than that in neutral environment. This suggests that MHApH 8.4 showed a more sustained release in acidic environment, which can be established by osteoclasts. The variation of adsorption strength between protein and MHA may be responsible for these behaviors. Our findings may be very useful for the development of MHA applications on both bone repair and protein delivery.