Biodegradable Polymer composites of MOF-5 for efficient and sustained delivery of cephalexin and metronidazole Anoff Anim 1 , Lila A. M. Mahmoud 2 , Maria Katsikogianni 1 and Sanjit Nayak 1 1 School of Chemistry and Biosciences, University of Bradford, Bradford, BD7 1DP, UK 2 School of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan Sustained and controlled delivery of antimicrobial drugs have been largely studied recently using metal organic frameworks (MOFs)and different polymers. However, much attention has not been given to combining both MOFs and biodegradable polymers which would be a good strategy in providing a sustained gradual release of the drugs. Herein, we report a comparative study of the sustained and controlled release of widely used antibacterial drugs, cephalexin and metronidazole, from zinc-based MOF-5 incorporated in biodegradable polycaprolactone (PCL) and poly-lactic glycolic acid (PLGA) membranes. Cephalexin and metronidazole were separately incorporated in MOF-5 post-synthetically, followed by their integration into biodegradable PLGA and PCL membranes. The pristine MOF-5 and the loaded MOFs were thoroughly characterized by FT-IR, SEM, TGA and PXRD. Drug release studies were carried out to assess the release rate of the drugs in PBS and distilled water for up to 48 hours using UV-Vis Spectroscopy. Four bacterial strains from both the Gram-positive and Gram- negative types, Staphylococus aureus , Staphylococuss epidermidis , Escherichia coli , Acinetobacter baumanii , were tested against the pristine MOF, pure drugs, loaded MOFs and the drug-loaded MOF-polymer composites. Metronidazole-loaded MOF-5 composite of PLGA (PLGA-Met@MOF-5) was found to show highest efficiency to inhibit the growth of S. epidermidis compared to the other bacteria strains while maintaining a sustained minimum inhibitory concentration (MIC). This study demonstrates that the combination of biodegradable MOF-polymer composites can provide an efficient platform for sustained and controlled release of antimicrobial drugs, and can be a potential strategy to integrate them in biomedical devices. References 1. de Kraker MEA, Stewardson AJ, Harbarth S. Will 10 Million People Die a Year due to Antimicrobial Resistance by 2050? PLoS medicine 2016;13:e1002184-e84. 2. Zhang W, Hu Y, Ma L, Zhu G, Wang Y, Xue X, et al. Progress and Perspective of Electrocatalytic CO2 Reduction for Renewable Carbonaceous Fuels and Chemicals. Advanced science 2018;5:n/a-n/a. 3. Otsubo K, Haraguchi T, Kitagawa H. Nanoscale crystalline architectures of Hofmann-type metal–organic frameworks. Coordination chemistry reviews 2017;346:123-38. 4. Wang C, Xie Z, deKrafft KE, Lin W, Energy Frontier Research Centers . Center for Solar F. Doping Metal–Organic Frameworks for Water Oxidation, Carbon Dioxide Reduction, and Organic Photocatalysis. Journal of the American Chemical Society 2011;133. 5. Guo H, Zhu S, Cai D, Liu C. Fabrication of ITO glass supported Tb-MOF film for sensing organic solvent. Inorganic chemistry communications 2014;41:29-32. 6. Osterrieth JWM, Fairen‐Jimenez D. Metal–Organic Framework Composites for Theragnostics and Drug Delivery Applications. Biotechnology journal 2021;16:e2000005-n/a.
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