New mixed-ligand Zn()-based MOF as a nanocarrier platform for improved antibacterial activity of clinically approved drug levofloxacin

The advancement of metal-organic frameworks (MOFs) operating as drug delivery systems is of extensive interest as their controlled drug release and specific delivery are very propitious. Herein, we report a new metal-organic framework (Zn-nMOF) formulated from a mixed ligand system comprising 5-hydroxyisophthalate ions ( L 1 ) and 5,5′-dimethyl-2,2′-bipyridine ( L 2 ) with zinc ions serving as metal centers. The crystal structure of the synthesized MOF was determined by single-crystal X-ray analysis and further supported by FTIR, PXRD, TEM, SEM, EDX, and UV/visible spectroscopy. The loading of a clinically approved broad-spectrum drug levofloxacin onto this zinc-based MOF was achieved by activating the pendent hydroxyl groups of the organic linker (5-hydroxyisophthalic acid) onto the surface of the MOF using the activator 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). The confirmation of successful conjugation of levofloxacin onto the MOF and formation of Levo@Zn-nMOF was well supported by FTIR, UV/visible, SEM, and EDX techniques. The levofloxacin-conjugated Zn-nMOF (Levo@Zn-nMOF) showed increased antibacterial efficacy compared to pure levofloxacin against Gram-positive and Gram-negative bacteria, specifically S. aureus (MIC-64.4 μg mL −1 ), B. subtilis (MIC-94.97 μg mL −1 ), E. coli (MIC-26.0 μg mL −1 ), and P. aeruginosa (MIC-67.48 μg mL −1 ). The efficiency of conjugated levofloxacin showed improvement by 1.65 times, 1.71 times, 1.56 times, and 1.03 times in S. aureus , B. subtilis , E. coli , and P. aeruginosa , respectively. This work shows that a significant increase in antibacterial efficacy can be achieved for certain antibiotics by conjugating them to the MOF surface through a covalent bond linkage. The advancement of metal-organic frameworks (MOFs) operating as drug delivery systems is of extensive interest as their controlled drug release and specific delivery are very propitious.