Sorption Studies of Tetracycline Antibiotics on Hydroxyapatite (001) Surface—A First-Principles Insight

Abstract

Owing to the limitations of traditional systemic drug delivery in the treatment of bone diseases with side effects on normal cells, the selection of materials with high affinities for bones, as targeting ligands to modify drug carriers, has become an important research topic. Tetracyclines (TCs) have an adsorption effect on hydroxyapatite (HAp). Thus, they can be used as bone-targeting ligands and combined with drug carriers. In this study, density functional theory is used to analyze the interaction mechanism of TC, oxytetracycline (OTC), chlortetracycline, and HAp. We calculate the electrostatic potential (ESP) and molecular orbitals to predict the possible binding sites of TCs on the HAp surface. The adsorption energy is used to compare the affinities of the three TCs to HAp. An independent gradient model analysis is performed to study the weak interaction between TCs and HAp. The coordination bond between TCs and the HAp surface is evaluated by conducting a charge density difference analysis. The results show that OTC has the highest affinity to HAp because the introduction of hydroxyl groups change the adsorption configuration of OTC. Thus, OTC adsorbed on HAp in a broken-line shape exposes more binding sites. This study provides a theoretical basis for TCs as bone-targeting ligands in treating bone diseases and in improving the safety of treatment by selecting different bone-targeting ligands.

Perspective Chapter: Hydroxyapatite – Surface Functionalization to Prevent Bacterial Colonization

“…The nature and chemistry of the HA control the interaction with biomolecules, and the surface chemistry and porosity are fundamental variables. The interaction between adsorbed molecules and hydroxyapatite surfaces is predominantly Van der Waals forces, hydrogen, and weak coordination bonds [78].…”

“…Other fluoroquinolones, such as enoxacin, have been employed together with nano-HA/Polyurethane-cement to enhance the antibacterial properties of bone cement [109]. Adsorption has been used to introduce broadspectrum antibiotics of the tetracycline class and cyclic oligosaccharides, such as cyclodextrin, onto HA surfaces [78,88,95]. Moreover, antibiotics from the glycopeptides class as vancomycin has been loaded into porous substrates to obtain a controlled release [84,91].…”

Paradoxical role of reactive oxygen species in bone remodelling: implications in osteoporosis and possible nanotherapeutic interventions

“…Some mineral-based therapies have been demonstrated to accomplish new bone formation by downregulating the osteoclast activity. The nano-hydroxyapatite (nano-HA) crystal further has the potential to combat osteoporosis as reported in in vivo study suggesting its role in initiating bone formation to the point of healing [85].…”

“…Therefore, use of this antibiotic was discontinued in paediatric regimens. Song et al [85] have reported the targeting mechanisms for tetracycline and its derivative to HA surface and resolved the issues of the nonspecific binding to bone in an in vitro model, but it has not been validated in any biological model as yet [92]. Unlike tetracycline, bisphosphonates have emerged as attractive targeting molecules in recent years, as they are widely used due to their strong affinity to bind with HA and can be exploited in the treatment of osteoporosis and bone osteolytic disease.…”

Strontium-doped apatitic bone cements with tunable antibacterial and antibiofilm ability

“…The development of scaffolds for the regeneration of bone defects has been a major research target in the orthopedic field in the last decades, especially given the steady rise of traumas or metabolic diseases such as osteoporosis and bone tumors (Sohn and Oh, 2019;Reid, 2020;Zhao et al, 2021). Biomaterials based on calcium phosphates and hydroxyapatite (HA), are widely considered as elective for the development of bone scaffolds, due to their high chemical similarity with the mineral phase of bone tissue, which is a key aspect to promote new bone formation (Jeong et al, 2019;Lodoso-Torrecilla et al, 2021;Tavoni et al, 2021).…”