Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin

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 <i>Staphylococcus aureus</i> osteomyelitis, localized antibiotic del...

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Main Authors: Luke J. Tucker, Christine S. Grant, Malley A. Gautreaux, Dhanush L. Amarasekara, Nicholas C. Fitzkee, Amol V. Janorkar, Anandavalli Varadarajan, Santanu Kundu, Lauren B. Priddy
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/19/3/144
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author Luke J. Tucker
Christine S. Grant
Malley A. Gautreaux
Dhanush L. Amarasekara
Nicholas C. Fitzkee
Amol V. Janorkar
Anandavalli Varadarajan
Santanu Kundu
Lauren B. Priddy
author_facet Luke J. Tucker
Christine S. Grant
Malley A. Gautreaux
Dhanush L. Amarasekara
Nicholas C. Fitzkee
Amol V. Janorkar
Anandavalli Varadarajan
Santanu Kundu
Lauren B. Priddy
author_sort Luke J. Tucker
collection DOAJ
description 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 <i>Staphylococcus aureus</i> 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 <i>S. aureus</i>, 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.
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spelling doaj.art-3783a64bae144b0d8c08a92afdf208d42023-12-03T12:50:19ZengMDPI AGMarine Drugs1660-33972021-03-0119314410.3390/md19030144Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with FosfomycinLuke J. Tucker0Christine S. Grant1Malley A. Gautreaux2Dhanush L. Amarasekara3Nicholas C. Fitzkee4Amol V. Janorkar5Anandavalli Varadarajan6Santanu Kundu7Lauren B. Priddy8Department of Agricultural and Biological Engineering, Mississippi State University, Mississippi State, MS 39762, USADepartment of Agricultural and Biological Engineering, Mississippi State University, Mississippi State, MS 39762, USADepartment of Agricultural and Biological Engineering, Mississippi State University, Mississippi State, MS 39762, USADepartment of Chemistry, Mississippi State University, Mississippi State, MS 39762, USADepartment of Chemistry, Mississippi State University, Mississippi State, MS 39762, USADepartment of Biomedical Materials Science, University of Mississippi Medical Center, Jackson, MS 39216, USADepartment of Chemical Engineering, Mississippi State University, Mississippi State, MS 39762, USADepartment of Chemical Engineering, Mississippi State University, Mississippi State, MS 39762, USADepartment of Agricultural and Biological Engineering, Mississippi State University, Mississippi State, MS 39762, USAThermosensitive 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 <i>Staphylococcus aureus</i> 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 <i>S. aureus</i>, 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.https://www.mdpi.com/1660-3397/19/3/144fosfomycinchitosanhydrogel<i>S. aureus</i>rheologyantimicrobial
spellingShingle Luke J. Tucker
Christine S. Grant
Malley A. Gautreaux
Dhanush L. Amarasekara
Nicholas C. Fitzkee
Amol V. Janorkar
Anandavalli Varadarajan
Santanu Kundu
Lauren B. Priddy
Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin
Marine Drugs
fosfomycin
chitosan
hydrogel
<i>S. aureus</i>
rheology
antimicrobial
title Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin
title_full Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin
title_fullStr Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin
title_full_unstemmed Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin
title_short Physicochemical and Antimicrobial Properties of Thermosensitive Chitosan Hydrogel Loaded with Fosfomycin
title_sort physicochemical and antimicrobial properties of thermosensitive chitosan hydrogel loaded with fosfomycin
topic fosfomycin
chitosan
hydrogel
<i>S. aureus</i>
rheology
antimicrobial
url https://www.mdpi.com/1660-3397/19/3/144
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