Gelatin Methacryloyl Hydrogels for the Localized Delivery of Cefazolin

The tuneability of hydrogels renders them promising candidates for local drug delivery to prevent and treat local surgical site infection (SSI) while avoiding the systemic side-effects of intravenous antibiotic injections. Here, we present a newly developed gelatin methacryloyl (GelMA)-based hydroge...

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Autores principales: Margaux Vigata, Cathal D. O’Connell, Silvia Cometta, Dietmar W. Hutmacher, Christoph Meinert, Nathalie Bock
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:d26694bab5be413ba0119dddfdea41482021-11-25T18:48:46ZGelatin Methacryloyl Hydrogels for the Localized Delivery of Cefazolin10.3390/polym132239602073-4360https://doaj.org/article/d26694bab5be413ba0119dddfdea41482021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4360/13/22/3960https://doaj.org/toc/2073-4360The tuneability of hydrogels renders them promising candidates for local drug delivery to prevent and treat local surgical site infection (SSI) while avoiding the systemic side-effects of intravenous antibiotic injections. Here, we present a newly developed gelatin methacryloyl (GelMA)-based hydrogel drug delivery system (GelMA-DDS) to locally deliver the broad-spectrum antibiotic cefazolin for SSI prophylaxis and treatment. Antibiotic doses from 3 µg to 90 µg were loaded in photocrosslinked GelMA hydrogel discs with 5 to 15% <i>w/v</i> polymer concentration and drug encapsulation efficiencies, mechanical properties, crosslinking and release kinetics, as well as bacterial growth inhibition were assessed. Our results demonstrate that all GelMA groups supported excellent drug encapsulation efficiencies of up to 99%. Mechanical properties of the GelMA-DDS were highly tuneable and unaffected by the loading of small to medium doses of cefazolin. The diffusive and the proteolytic in vitro drug delivery of all investigated cefazolin doses was characterized by a burst release, and the delivered cefazolin amount was directly proportional to the encapsulated dose. Accelerated enzymatic degradation of the GelMA-DDS followed zero-order kinetics and was dependent on both the cefazolin dose and GelMA concentration (3–13 h). Finally, we demonstrate that cefazolin delivered from GelMA induced a dose-dependent antibacterial efficacy against <i>S. aureus</i>, in both a broth and a diffusive assay. The cefazolin-loaded GelMA-DDS presented here provides a highly tuneable and easy-to-use local delivery system for the prophylaxis and treatment of SSI.Margaux VigataCathal D. O’ConnellSilvia ComettaDietmar W. HutmacherChristoph MeinertNathalie BockMDPI AGarticlegelatin methacryloylcefazolinlocalized antibiotic therapydrug deliverysurgery site infectionOrganic chemistryQD241-441ENPolymers, Vol 13, Iss 3960, p 3960 (2021)
institution DOAJ
collection DOAJ
language EN
topic gelatin methacryloyl
cefazolin
localized antibiotic therapy
drug delivery
surgery site infection
Organic chemistry
QD241-441
spellingShingle gelatin methacryloyl
cefazolin
localized antibiotic therapy
drug delivery
surgery site infection
Organic chemistry
QD241-441
Margaux Vigata
Cathal D. O’Connell
Silvia Cometta
Dietmar W. Hutmacher
Christoph Meinert
Nathalie Bock
Gelatin Methacryloyl Hydrogels for the Localized Delivery of Cefazolin
description The tuneability of hydrogels renders them promising candidates for local drug delivery to prevent and treat local surgical site infection (SSI) while avoiding the systemic side-effects of intravenous antibiotic injections. Here, we present a newly developed gelatin methacryloyl (GelMA)-based hydrogel drug delivery system (GelMA-DDS) to locally deliver the broad-spectrum antibiotic cefazolin for SSI prophylaxis and treatment. Antibiotic doses from 3 µg to 90 µg were loaded in photocrosslinked GelMA hydrogel discs with 5 to 15% <i>w/v</i> polymer concentration and drug encapsulation efficiencies, mechanical properties, crosslinking and release kinetics, as well as bacterial growth inhibition were assessed. Our results demonstrate that all GelMA groups supported excellent drug encapsulation efficiencies of up to 99%. Mechanical properties of the GelMA-DDS were highly tuneable and unaffected by the loading of small to medium doses of cefazolin. The diffusive and the proteolytic in vitro drug delivery of all investigated cefazolin doses was characterized by a burst release, and the delivered cefazolin amount was directly proportional to the encapsulated dose. Accelerated enzymatic degradation of the GelMA-DDS followed zero-order kinetics and was dependent on both the cefazolin dose and GelMA concentration (3–13 h). Finally, we demonstrate that cefazolin delivered from GelMA induced a dose-dependent antibacterial efficacy against <i>S. aureus</i>, in both a broth and a diffusive assay. The cefazolin-loaded GelMA-DDS presented here provides a highly tuneable and easy-to-use local delivery system for the prophylaxis and treatment of SSI.
format article
author Margaux Vigata
Cathal D. O’Connell
Silvia Cometta
Dietmar W. Hutmacher
Christoph Meinert
Nathalie Bock
author_facet Margaux Vigata
Cathal D. O’Connell
Silvia Cometta
Dietmar W. Hutmacher
Christoph Meinert
Nathalie Bock
author_sort Margaux Vigata
title Gelatin Methacryloyl Hydrogels for the Localized Delivery of Cefazolin
title_short Gelatin Methacryloyl Hydrogels for the Localized Delivery of Cefazolin
title_full Gelatin Methacryloyl Hydrogels for the Localized Delivery of Cefazolin
title_fullStr Gelatin Methacryloyl Hydrogels for the Localized Delivery of Cefazolin
title_full_unstemmed Gelatin Methacryloyl Hydrogels for the Localized Delivery of Cefazolin
title_sort gelatin methacryloyl hydrogels for the localized delivery of cefazolin
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/d26694bab5be413ba0119dddfdea4148
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AT cathaldoconnell gelatinmethacryloylhydrogelsforthelocalizeddeliveryofcefazolin
AT silviacometta gelatinmethacryloylhydrogelsforthelocalizeddeliveryofcefazolin
AT dietmarwhutmacher gelatinmethacryloylhydrogelsforthelocalizeddeliveryofcefazolin
AT christophmeinert gelatinmethacryloylhydrogelsforthelocalizeddeliveryofcefazolin
AT nathaliebock gelatinmethacryloylhydrogelsforthelocalizeddeliveryofcefazolin
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