Controlled delivery of ciprofloxacin using zirconium-based MOFs and poly-caprolactone composites

Abstract

With antimicrobial resistance (AMR) increasing at an alarming rate, there is a need to develop better antibiotic delivery platforms at the point of need, to reduce over-exposure to antibiotics that are delivered systemically. Recent studies have suggested the use of metal-organic frameworks (MOFs) as potential vehicles for controlled and efficient delivery of various active pharmaceutical ingredients (APIs). Development of MOF-polymer composite materials can assist in the development of medical devices that can deliver APIs to local sites in a targeted approach. This study reports the encapsulation of a widely used antibiotic - ciprofloxacin (CIP) - into two Zr-based MOFs (UiO-66 and UiO-66-NH2) and their subsequent integration into a biodegradable polymer; polycaprolactone (PCL), via solvent casting, to obtain a PCL-MOF composite membrane. The MOFs and PCL-MOF composites were characterised by Fourier-transformed infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The results demonstrated that the structural integrity of the pristine MOFs was maintained after drug loading and incorporation into the PCL membranes. The ciprofloxacin release was studied using ultraviolet–visible (UV–Vis) spectroscopy, and the results showed that the PCL-MOF composites had a more controlled drug release profile compared to the MOF alone, when monitored for seven days in phosphate buffered saline (PBS) and accelerated ageing (AA) release media. In addition, release studies showed pH-dependence with faster release of ciprofloxacin at both acidic and basic conditions. Antimicrobial assay showed excellent efficacy for both CIP-loaded MOFs and their PCL composites against S. aureus and E. coli, a Gram-negative and Gram-positive bacterium, respectively, with inhibition zone as high as >50 mm against E. coli for UiO-66-NH2-CIP, indicating their potential applications in purpose-specific medical devices.