Christine S. Grant

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.

With antibiotic‐resistant bacteria becoming increasingly prevalent, biomaterials capable of targeted, in situ drug delivery are urgently needed. The synthetic polymer Poloxamer 407 (P407) is of particular interest due to its thermoreversible gelation. Clinical use of P407 typically involves sterilization via autoclaving, but the effects of these extreme environmental conditions on hydrogel water content, rheological properties and efficacy as a drug delivery vehicle remain unknown. The aim of this study was to investigate the effects of autoclaving on the properties of P407 hydrogel. Autoclaving reduced hydrogel water content due to evaporation, thus increasing the polymer weight fraction of the hydrogels. In contrast, except for a reduction in gelation temperature following autoclaving, autoclaved hydrogels had similar rheological properties as nonautoclaved hydrogels. In vitro, autoclaving did not hinder the hydrogel's efficacy as a carrier for vancomycin antibiotic, and P407 (with and without vancomycin) had a bactericidal effect on planktonic Staphylococcus aureus. An in vivo pilot study using P407 to deliver bacteriophage highlighted the need for additional understanding of the functionality of the hydrogel for surgical applications. In conclusion, P407 hydrogel water content and gelation temperature were reduced by autoclave sterilization, while other rheological properties and the efficacy of the biomaterial as a delivery vehicle for vancomycin in vitro were unaffected.