Drug Delivery from Hyaluronic Acid–BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory Applications

Hyaluronic acid (HA) injectable biomaterials are currently applied in numerous biomedical areas, beyond their use as dermal fillers. However, bacterial infections and painful inflammations are associated with healthcare complications that can appear after injection, restricting their applicability....

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Main Authors: Jon Andrade del Olmo, Leyre Pérez-Álvarez, Virginia Sáez Martínez, Sandra Benito Cid, Raúl Pérez González, José Luis Vilas-Vilela, José María Alonso
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Gels
Subjects:
Online Access:https://www.mdpi.com/2310-2861/8/4/223
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author Jon Andrade del Olmo
Leyre Pérez-Álvarez
Virginia Sáez Martínez
Sandra Benito Cid
Raúl Pérez González
José Luis Vilas-Vilela
José María Alonso
author_facet Jon Andrade del Olmo
Leyre Pérez-Álvarez
Virginia Sáez Martínez
Sandra Benito Cid
Raúl Pérez González
José Luis Vilas-Vilela
José María Alonso
author_sort Jon Andrade del Olmo
collection DOAJ
description Hyaluronic acid (HA) injectable biomaterials are currently applied in numerous biomedical areas, beyond their use as dermal fillers. However, bacterial infections and painful inflammations are associated with healthcare complications that can appear after injection, restricting their applicability. Fortunately, HA injectable hydrogels can also serve as drug delivery platforms for the controlled release of bioactive agents with a critical role in the control of certain diseases. Accordingly, herein, HA hydrogels were crosslinked with 1 4-butanediol diglycidyl ether (BDDE) loaded with cefuroxime (CFX), tetracycline (TCN), and amoxicillin (AMX) antibiotics and acetylsalicylic acid (ASA) anti-inflammatory agent in order to promote antibacterial and anti-inflammatory responses. The hydrogels were thoroughly characterized and a clear correlation between the crosslinking grade and the hydrogels’ physicochemical properties was found after rheology, scanning electron microscopy (SEM), thermogravimetry (TGA), and differential scanning calorimetry (DSC) analyses. The biological safety of the hydrogels, expected due to the lack of BDDE residues observed in <sup>1</sup>H-NMR spectroscopy, was also corroborated by an exhaustive biocompatibility test. As expected, the in vitro antibacterial and anti-inflammatory activity of the drug-loaded HA-BDDE hydrogels was confirmed against <i>Staphylococcus aureus</i> by significantly decreasing the pro-inflammatory cytokine levels.
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spelling doaj.art-a34c192e01414b37ae3f120aeb2ffed62023-12-01T20:55:58ZengMDPI AGGels2310-28612022-04-018422310.3390/gels8040223Drug Delivery from Hyaluronic Acid–BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory ApplicationsJon Andrade del Olmo0Leyre Pérez-Álvarez1Virginia Sáez Martínez2Sandra Benito Cid3Raúl Pérez González4José Luis Vilas-Vilela5José María Alonso6i+Med S. Coop. Parque Tecnológico de Álava, Albert Einstein 15, Nave 15, 01510 Vitoria-Gasteiz, SpainGrupo de Química Macromolecular (LABQUIMAC), Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco UPV/EHU, 48940 Leioa, Spaini+Med S. Coop. Parque Tecnológico de Álava, Albert Einstein 15, Nave 15, 01510 Vitoria-Gasteiz, Spaini+Med S. Coop. Parque Tecnológico de Álava, Albert Einstein 15, Nave 15, 01510 Vitoria-Gasteiz, Spaini+Med S. Coop. Parque Tecnológico de Álava, Albert Einstein 15, Nave 15, 01510 Vitoria-Gasteiz, SpainGrupo de Química Macromolecular (LABQUIMAC), Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco UPV/EHU, 48940 Leioa, Spaini+Med S. Coop. Parque Tecnológico de Álava, Albert Einstein 15, Nave 15, 01510 Vitoria-Gasteiz, SpainHyaluronic acid (HA) injectable biomaterials are currently applied in numerous biomedical areas, beyond their use as dermal fillers. However, bacterial infections and painful inflammations are associated with healthcare complications that can appear after injection, restricting their applicability. Fortunately, HA injectable hydrogels can also serve as drug delivery platforms for the controlled release of bioactive agents with a critical role in the control of certain diseases. Accordingly, herein, HA hydrogels were crosslinked with 1 4-butanediol diglycidyl ether (BDDE) loaded with cefuroxime (CFX), tetracycline (TCN), and amoxicillin (AMX) antibiotics and acetylsalicylic acid (ASA) anti-inflammatory agent in order to promote antibacterial and anti-inflammatory responses. The hydrogels were thoroughly characterized and a clear correlation between the crosslinking grade and the hydrogels’ physicochemical properties was found after rheology, scanning electron microscopy (SEM), thermogravimetry (TGA), and differential scanning calorimetry (DSC) analyses. The biological safety of the hydrogels, expected due to the lack of BDDE residues observed in <sup>1</sup>H-NMR spectroscopy, was also corroborated by an exhaustive biocompatibility test. As expected, the in vitro antibacterial and anti-inflammatory activity of the drug-loaded HA-BDDE hydrogels was confirmed against <i>Staphylococcus aureus</i> by significantly decreasing the pro-inflammatory cytokine levels.https://www.mdpi.com/2310-2861/8/4/223hyaluronic acidinjectable hydrogelsbiocompatibilitydrug deliveryantibacterialanti-inflammatory
spellingShingle Jon Andrade del Olmo
Leyre Pérez-Álvarez
Virginia Sáez Martínez
Sandra Benito Cid
Raúl Pérez González
José Luis Vilas-Vilela
José María Alonso
Drug Delivery from Hyaluronic Acid–BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory Applications
Gels
hyaluronic acid
injectable hydrogels
biocompatibility
drug delivery
antibacterial
anti-inflammatory
title Drug Delivery from Hyaluronic Acid–BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory Applications
title_full Drug Delivery from Hyaluronic Acid–BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory Applications
title_fullStr Drug Delivery from Hyaluronic Acid–BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory Applications
title_full_unstemmed Drug Delivery from Hyaluronic Acid–BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory Applications
title_short Drug Delivery from Hyaluronic Acid–BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory Applications
title_sort drug delivery from hyaluronic acid bdde injectable hydrogels for antibacterial and anti inflammatory applications
topic hyaluronic acid
injectable hydrogels
biocompatibility
drug delivery
antibacterial
anti-inflammatory
url https://www.mdpi.com/2310-2861/8/4/223
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