Synthesis and Characterization of Antibiotic-Loaded Biodegradable Citrate Functionalized Mesoporous Hydroxyapatite Nanocarriers as an Alternative Treatment for Bone Infections

Pharmaceutics. 2022 Apr 30;14(5):975. doi: 10.3390/pharmaceutics14050975.

Abstract

The continuing growth of bacterial resistance makes the top challenge for the healthcare system especially in bone-infections treatment. Current estimates reveal that in 2050 the death ratio caused by bacterial infections can be higher than cancer. The aim of this study is to provide an alternative to currently available bone-infection treatments. Here we designed mesoporous hydroxyapatite nanocarriers functionalized with citrate (Ctr-mpHANCs). Amoxicillin (AMX) is used as a model drug to load in Ctr-mpHANCs, and the drug loading was more than 90% due to the porous nature of nanocarriers. Scanning electron microscopy shows the roughly spherical morphology of nanocarriers, and the DLS study showed the approximate size of 92 nm. The Brunauer-Emmett-Teller (BET) specific surface area and pore diameter was found to be about 182.35 m2/g and 4.2 nm, respectively. We noticed that almost 100% of the drug is released from the AMX loaded Ctr-mpHANCs (AMX@Ctr-mpHANCs) in a pH-dependent manner within 3 d and 5 d at pH 2.0 and 4.5, respectively. The sustained drug release behaviour was observed for 15 d at pH 7.4 and no RBCs hemolysis by AMX@Ctr-mpHANCs. The broth dilution and colony forming unit (CFU) assays were used to determine the antimicrobial potential of AMX@Ctr-mpHANCs. It was observed in both studies that AMX@Ctr-mpHANCs showed a significant reduction in the bacterial growth of S. aureus, E. coli, and P. aeruginosa as compared to Ctr-mpHANCs with no bacteria-killing. Thus, we proposed that Ctr-mpHANCs can be used as a drug carrier and a treatment option for bone infections caused by bacteria.

Keywords: antibiotic; bacterial resistance; bone infection; calcium phosphate; hydroxyapatite; multidrug resistance; nanocarrier.