Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin

Abstract

Thermosensitive chitosan hydrogels—renewable, biocompatible materials—have many applications as injectable biomaterials for localized drug delivery in the treatment of a variety of diseases. To combat infections such as Staphylococcus aureus osteomyelitis, localized antibiotic delivery would allow for higher doses at the site of infection without the risks associated with traditional antibiotic regimens. Fosfomycin, a small antibiotic in its own class, was loaded into a chitosan hydrogel system with varied beta-glycerol phosphate (β-GP) and fosfomycin (FOS) concentrations. The purpose of this study was to elucidate the interactions between FOS and chitosan hydrogel. The Kirby Bauer assay revealed an unexpected concentration-dependent inhibition of S. aureus, with reduced efficacy at the high FOS concentration but only at the low β-GP concentration. No effect of FOS concentration was observed for the planktonic assay. Rheological testing revealed that increasing β-GP concentration increased the storage modulus while decreasing gelation temperature. NMR showed that FOS was removed from the liquid portion of the hydrogel by reaction over 12 h. SEM and FTIR confirmed gels degraded and released organophosphates over 5 days. This work provides insight into the physicochemical interactions between fosfomycin and chitosan hydrogel systems and informs selection of biomaterial components for improving infection treatment.

Evaluation of an Injectable Hydrogel Based on Hyaluronic Acid–Chitosan/β‐Glycerophosphate‐Loaded Mesenchymal Stem Cells in Enhancing the Therapeutic Efficacy of Myocardial Infarction

“…Compared with CS and HA–CS, the β ‐GP‐loaded HA–CS hydrogel (HA–CS/ β ‐GP) exerted a considerable killing effect on both bacterial strains. [ 42 ] Furthermore, it was observed that the bacteriostatic activity of the HA–CS/ β ‐GP in this study was stronger against E. coli than against S. aureus most probably because of the differences in the membrane architectures of the two bacteria, which enlarged the inhibition zone. The antibacterial activity of β ‐GP might have been mediated via two different pathways: the first process involves the binding of β ‐GP to bacterial cell membranes to induce cell lysis, [ 43 ] and the second process entails β ‐GP extending the lag phase of these microorganisms to increase the duration between cell divisions.…”

Design of a Zr-based metal–organic framework as an efficient fosfomycin carrier: a combined experimental and DFT study

“…The peaks at 1050 cm À1 (1047 cm À1 , l = 1.00) and 981 cm À1 (1024 cm À1 , l = 0.96) are assigned to P-O stretching vibrations. 22 These peaks ascribed to P-O vibrations in FOS appear in the spectrum of UiO-66/FOS-AD as a broad band around 988 cm À1 (990 cm À1 , l = 1.00) due to the formation of a new Zr-O bond signifying that FOS has been successfully loaded on UiO-66 by adsorption. The appearance of this broad band clearly indicates the capture of FOS molecules by the adsorption and formation of a Zr-O-P complex, in accordance with our PXRD results and DFT calculations.…”

“…21 In a recent study, Tucker et al have loaded fosfomycin in chitosan hydrogels, and observed beneficial effects for infection control in vivo . 22 Recently, we have demonstrated the double function of UiO-66 in 3D chitosan scaffolds as a carrier for fosfomycin and also as an osteogenic differentiation promoter. UiO-66 nanocrystals were proved to possess a twofer character that would enrich their use in the biomedical field.…”