Anti-Inflammatory Properties of Injectable Betamethasone-Loaded Tyramine-Modified Gellan Gum/Silk Fibroin Hydrogels

Rheumatoid arthritis is a rheumatic disease for which a healing treatment does not presently exist. Silk fibroin has been extensively studied for use in drug delivery systems due to its uniqueness, versatility and strong clinical track record in medicine. However, in general, natural polymeric mater...

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Main Authors: Isabel Matos Oliveira, Cristiana Gonçalves, Myeong Eun Shin, Sumi Lee, Rui Luis Reis, Gilson Khang, Joaquim Miguel Oliveira
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/10/10/1456
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spelling doaj-d16336966a1645ac9b2c0234a6eb530e2020-11-25T03:53:57ZengMDPI AGBiomolecules2218-273X2020-10-01101456145610.3390/biom10101456Anti-Inflammatory Properties of Injectable Betamethasone-Loaded Tyramine-Modified Gellan Gum/Silk Fibroin HydrogelsIsabel Matos Oliveira0Cristiana Gonçalves1Myeong Eun Shin2Sumi Lee3Rui Luis Reis4Gilson Khang5Joaquim Miguel Oliveira63B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, Portugal3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, PortugalDepartment of BIN Fusion Technology, Department of Polymer Nanoscience and Polymer BIN Research Centre, Chonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju 561-756, KoreaDepartment of BIN Fusion Technology, Department of Polymer Nanoscience and Polymer BIN Research Centre, Chonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju 561-756, Korea3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, PortugalDepartment of BIN Fusion Technology, Department of Polymer Nanoscience and Polymer BIN Research Centre, Chonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju 561-756, Korea3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark, Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, 4805-017 Guimarães, PortugalRheumatoid arthritis is a rheumatic disease for which a healing treatment does not presently exist. Silk fibroin has been extensively studied for use in drug delivery systems due to its uniqueness, versatility and strong clinical track record in medicine. However, in general, natural polymeric materials are not mechanically stable enough, and have high rates of biodegradation. Thus, synthetic materials such as gellan gum can be used to produce composite structures with biological signals to promote tissue-specific interactions while providing the desired mechanical properties. In this work, we aimed to produce hydrogels of tyramine-modified gellan gum with silk fibroin (Ty–GG/SF) via horseradish peroxidase (HRP), with encapsulated betamethasone, to improve the biocompatibility and mechanical properties, and further increase therapeutic efficacy to treat rheumatoid arthritis (RA). The Ty–GG/SF hydrogels presented a β-sheet secondary structure, with gelation time around 2–5 min, good resistance to enzymatic degradation, a suitable injectability profile, viscoelastic capacity with a significant solid component and a betamethasone-controlled release profile over time. In vitro studies showed that Ty–GG/SF hydrogels did not produce a deleterious effect on cellular metabolic activity, morphology or proliferation. Furthermore, Ty–GG/SF hydrogels with encapsulated betamethasone revealed greater therapeutic efficacy than the drug applied alone. Therefore, this strategy can provide an improvement in therapeutic efficacy when compared to the traditional use of drugs for the treatment of rheumatoid arthritis.https://www.mdpi.com/2218-273X/10/10/1456Ty–GG/SF hydrogelsenzymatic crosslinkingbetamethasoneinflammationrheumatoid arthritis
collection DOAJ
language English
format Article
sources DOAJ
author Isabel Matos Oliveira
Cristiana Gonçalves
Myeong Eun Shin
Sumi Lee
Rui Luis Reis
Gilson Khang
Joaquim Miguel Oliveira
spellingShingle Isabel Matos Oliveira
Cristiana Gonçalves
Myeong Eun Shin
Sumi Lee
Rui Luis Reis
Gilson Khang
Joaquim Miguel Oliveira
Anti-Inflammatory Properties of Injectable Betamethasone-Loaded Tyramine-Modified Gellan Gum/Silk Fibroin Hydrogels
Biomolecules
Ty–GG/SF hydrogels
enzymatic crosslinking
betamethasone
inflammation
rheumatoid arthritis
author_facet Isabel Matos Oliveira
Cristiana Gonçalves
Myeong Eun Shin
Sumi Lee
Rui Luis Reis
Gilson Khang
Joaquim Miguel Oliveira
author_sort Isabel Matos Oliveira
title Anti-Inflammatory Properties of Injectable Betamethasone-Loaded Tyramine-Modified Gellan Gum/Silk Fibroin Hydrogels
title_short Anti-Inflammatory Properties of Injectable Betamethasone-Loaded Tyramine-Modified Gellan Gum/Silk Fibroin Hydrogels
title_full Anti-Inflammatory Properties of Injectable Betamethasone-Loaded Tyramine-Modified Gellan Gum/Silk Fibroin Hydrogels
title_fullStr Anti-Inflammatory Properties of Injectable Betamethasone-Loaded Tyramine-Modified Gellan Gum/Silk Fibroin Hydrogels
title_full_unstemmed Anti-Inflammatory Properties of Injectable Betamethasone-Loaded Tyramine-Modified Gellan Gum/Silk Fibroin Hydrogels
title_sort anti-inflammatory properties of injectable betamethasone-loaded tyramine-modified gellan gum/silk fibroin hydrogels
publisher MDPI AG
series Biomolecules
issn 2218-273X
publishDate 2020-10-01
description Rheumatoid arthritis is a rheumatic disease for which a healing treatment does not presently exist. Silk fibroin has been extensively studied for use in drug delivery systems due to its uniqueness, versatility and strong clinical track record in medicine. However, in general, natural polymeric materials are not mechanically stable enough, and have high rates of biodegradation. Thus, synthetic materials such as gellan gum can be used to produce composite structures with biological signals to promote tissue-specific interactions while providing the desired mechanical properties. In this work, we aimed to produce hydrogels of tyramine-modified gellan gum with silk fibroin (Ty–GG/SF) via horseradish peroxidase (HRP), with encapsulated betamethasone, to improve the biocompatibility and mechanical properties, and further increase therapeutic efficacy to treat rheumatoid arthritis (RA). The Ty–GG/SF hydrogels presented a β-sheet secondary structure, with gelation time around 2–5 min, good resistance to enzymatic degradation, a suitable injectability profile, viscoelastic capacity with a significant solid component and a betamethasone-controlled release profile over time. In vitro studies showed that Ty–GG/SF hydrogels did not produce a deleterious effect on cellular metabolic activity, morphology or proliferation. Furthermore, Ty–GG/SF hydrogels with encapsulated betamethasone revealed greater therapeutic efficacy than the drug applied alone. Therefore, this strategy can provide an improvement in therapeutic efficacy when compared to the traditional use of drugs for the treatment of rheumatoid arthritis.
topic Ty–GG/SF hydrogels
enzymatic crosslinking
betamethasone
inflammation
rheumatoid arthritis
url https://www.mdpi.com/2218-273X/10/10/1456
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