Professor Chang Gung University Taoyuan, Taiwan (Republic of China)
Introduction:: Metal–organic frameworks (MOFs) have been widely used as drug carriers owing to their tunable pore size, high surface area, potential further chemical fuctionalization, and excellent design ability. Compared with conventional antibacterial agents, MOF-based nanomaterials have specific benefits such as bactericidal metal ions (e.g., Ag+, Ca2+, Sr2+) along with certain organic antimicrobials/natural bioantimicrobials (e.g., porphyrins and imidazoles) are suitable for fabricating MOFs. In addition, calcium and strontium are important elements of synthetic hydroxyapatite (HAP) for bone regeneration, if antibacterial drug-containing particles can be incorporated into Ca/Sr-HAP, the potential for infection will be reduced. Therefore, in the present study, we aimed to synthesize Ca-Sr-MOFs for use in drug delivery systems. Furthermore, aminomalononitrile (AMN) coatings are a simple and versatile platform for biomolecule immobilization. To further evaluate the properties of Ca-Sr-MOF as drug carriers, the antibiotic drug tetracycline (TC) was incorporated, and the drug release of TC was evaluated.
Materials and Methods:: In this study, a Ca-Sr MOF was prepared by a simple precipitation method. In brief, sodium hydroxide (10 M) was added to a H3BTC solution (100 mg/ml) and then the pH was adjusted to neutral. Afterward, the solution was mixed with a solution containing calcium and strontium salts, then kept at room temperature for 3 days for for the crystallization of Ca-Sr-MOF. The AMN solution was prepared by dissolving AMN and THBA at final concentrations of 2.76 mM and 11.8 mM in phosphate buffer solution (pH 8.5), respectively. After mixing the Ca-Sr-MOF solution with the AMN solution, the resulting mixture was left at room temperature for 24 hours, leading to the formation of Ca-Sr-MOF crystals coated with AMN. The prepared Ca-Sr-MOF and Ca-Sr-AMN-MOF were characterized by fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HR-TEM) and UV‒visible spectroscopy. TC was selected as the model drug to measure the drug loading efficiency and release profile.
Results, Conclusions, and Discussions:: In this study, Ca-Sr-MOF and Ca-Sr-AMN-MOF were prepared by a precipitation method. Then, both prepared Ca-Sr-MOF and Ca-Sr-AMN-MOF were completely characterized by FTIR, PXRD, SEM, TEM, and UV‒visible spectroscopy. Successful TC incorporation onto Ca-Sr-MOF and Ca-Sr-AMN-MOF was confirmed by FTIR and UV‒visible spectroscopy. Furthermore, the cumulative drug release of TC from TC-Ca-Sr-MOF and TC-Ca-Sr-AMN-MOF was 55.2% and 9.1%,, respectively, after 24 hours. In addition, by performing an MTT assay, both the MOF and TC-loaded MOF have no significant cytotoxicity. Together, these results show that Ca-Sr-MOF and Ca-Sr-AMN-MOF prepared in the study have potential for biomedical applications.
Acknowledgements (Optional): : The present research was supported by Chang Gung Memorial Hospital, grant numbers CMRPD2K0152 and National Science and Technology Council, grant numbers 110-2314-B-182-011-MY2