Ca-Alginate-PEGMA Hydrogels for In Situ Delivery of TGF-β Neutralizing Antibodies in a Mouse Model of Wound Healing

Hydrogels provide effective alternatives for drug delivery when therapeutics cannot be applied directly to a wound, or if adverse effects are associated with systemic administration. However, drug delivery vehicles need to be biocompatible and biodegradable and exhibit sufficient mechanical strength...

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Main Authors: Jahaziel Gasperin-Bulbarela, Ana B. Castro-Ceseña, Tanya Camacho-Villegas, Pavel H. Lugo-Fabres, Nestor Emmanuel Díaz-Martínez, Eduardo Padilla-Camberos, Raquel Echavarría, Alexei F. Licea-Navarro
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Applied Sciences
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Online Access:https://www.mdpi.com/2076-3417/11/3/1164
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author Jahaziel Gasperin-Bulbarela
Ana B. Castro-Ceseña
Tanya Camacho-Villegas
Pavel H. Lugo-Fabres
Nestor Emmanuel Díaz-Martínez
Eduardo Padilla-Camberos
Raquel Echavarría
Alexei F. Licea-Navarro
author_facet Jahaziel Gasperin-Bulbarela
Ana B. Castro-Ceseña
Tanya Camacho-Villegas
Pavel H. Lugo-Fabres
Nestor Emmanuel Díaz-Martínez
Eduardo Padilla-Camberos
Raquel Echavarría
Alexei F. Licea-Navarro
author_sort Jahaziel Gasperin-Bulbarela
collection DOAJ
description Hydrogels provide effective alternatives for drug delivery when therapeutics cannot be applied directly to a wound, or if adverse effects are associated with systemic administration. However, drug delivery vehicles need to be biocompatible and biodegradable and exhibit sufficient mechanical strength to withstand handling and different physiological conditions, such as those encountered during topical administration of a therapeutic. Wound healing can be divided into three phases stimulated by transforming growth factor-beta (TGF-β) and, subsequently, targeted therapeutics have been developed to inhibit this cytokine for the treatment of chronic wounds and to prevent scarring. In this study, the capacity of calcium alginate hydrogels plasticized with poly(ethylene glycol) methyl ether methacrylate (PEGMA) to deliver anti-TGF-β antibodies (1D11.16.8) to a wound was investigated in situ. Three levels of antibodies, 10, 50, and 100 μg, were loaded into calcium-alginate-PEGMA hydrogels and evaluated in an excisional wound model in mice. Hydrogels containing 50 and 100 μg 1D11.16.8 produced less inflammation, accompanied by a marked reduction in collagen deposition and cell infiltration. These findings demonstrate the capacity of calcium-alginate-PEGMA hydrogels to deliver larger proteins, such as antibodies, to the site of a wound.
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spelling doaj.art-e7573d363e3a4e4b89a8a7126c5b74982023-12-03T14:53:42ZengMDPI AGApplied Sciences2076-34172021-01-01113116410.3390/app11031164Ca-Alginate-PEGMA Hydrogels for In Situ Delivery of TGF-β Neutralizing Antibodies in a Mouse Model of Wound HealingJahaziel Gasperin-Bulbarela0Ana B. Castro-Ceseña1Tanya Camacho-Villegas2Pavel H. Lugo-Fabres3Nestor Emmanuel Díaz-Martínez4Eduardo Padilla-Camberos5Raquel Echavarría6Alexei F. Licea-Navarro7Departamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Carretera Ensenada-Tijuana No. 3918, Zona Playitas, Ensenada C.P. 22860, Baja California, MexicoDepartamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Carretera Ensenada-Tijuana No. 3918, Zona Playitas, Ensenada C.P. 22860, Baja California, MexicoUnidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), A.C. Av. Normalistas 800 Colinas de la Normal, Guadalajara C.P. 44270, Jalisco, MexicoUnidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), A.C. Av. Normalistas 800 Colinas de la Normal, Guadalajara C.P. 44270, Jalisco, MexicoUnidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), A.C. Av. Normalistas 800 Colinas de la Normal, Guadalajara C.P. 44270, Jalisco, MexicoUnidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), A.C. Av. Normalistas 800 Colinas de la Normal, Guadalajara C.P. 44270, Jalisco, MexicoCONACyT-Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara C.P. 44340, Jalisco, MexicoDepartamento de Innovación Biomédica, Centro de Investigación Científica y de Educación Superior de Ensenada (CICESE), Carretera Ensenada-Tijuana No. 3918, Zona Playitas, Ensenada C.P. 22860, Baja California, MexicoHydrogels provide effective alternatives for drug delivery when therapeutics cannot be applied directly to a wound, or if adverse effects are associated with systemic administration. However, drug delivery vehicles need to be biocompatible and biodegradable and exhibit sufficient mechanical strength to withstand handling and different physiological conditions, such as those encountered during topical administration of a therapeutic. Wound healing can be divided into three phases stimulated by transforming growth factor-beta (TGF-β) and, subsequently, targeted therapeutics have been developed to inhibit this cytokine for the treatment of chronic wounds and to prevent scarring. In this study, the capacity of calcium alginate hydrogels plasticized with poly(ethylene glycol) methyl ether methacrylate (PEGMA) to deliver anti-TGF-β antibodies (1D11.16.8) to a wound was investigated in situ. Three levels of antibodies, 10, 50, and 100 μg, were loaded into calcium-alginate-PEGMA hydrogels and evaluated in an excisional wound model in mice. Hydrogels containing 50 and 100 μg 1D11.16.8 produced less inflammation, accompanied by a marked reduction in collagen deposition and cell infiltration. These findings demonstrate the capacity of calcium-alginate-PEGMA hydrogels to deliver larger proteins, such as antibodies, to the site of a wound.https://www.mdpi.com/2076-3417/11/3/1164hydrogelwound healingCa-alginatepoly(ethylene glycol) methyl ether methacrylate1D11TGF-β
spellingShingle Jahaziel Gasperin-Bulbarela
Ana B. Castro-Ceseña
Tanya Camacho-Villegas
Pavel H. Lugo-Fabres
Nestor Emmanuel Díaz-Martínez
Eduardo Padilla-Camberos
Raquel Echavarría
Alexei F. Licea-Navarro
Ca-Alginate-PEGMA Hydrogels for In Situ Delivery of TGF-β Neutralizing Antibodies in a Mouse Model of Wound Healing
Applied Sciences
hydrogel
wound healing
Ca-alginate
poly(ethylene glycol) methyl ether methacrylate
1D11
TGF-β
title Ca-Alginate-PEGMA Hydrogels for In Situ Delivery of TGF-β Neutralizing Antibodies in a Mouse Model of Wound Healing
title_full Ca-Alginate-PEGMA Hydrogels for In Situ Delivery of TGF-β Neutralizing Antibodies in a Mouse Model of Wound Healing
title_fullStr Ca-Alginate-PEGMA Hydrogels for In Situ Delivery of TGF-β Neutralizing Antibodies in a Mouse Model of Wound Healing
title_full_unstemmed Ca-Alginate-PEGMA Hydrogels for In Situ Delivery of TGF-β Neutralizing Antibodies in a Mouse Model of Wound Healing
title_short Ca-Alginate-PEGMA Hydrogels for In Situ Delivery of TGF-β Neutralizing Antibodies in a Mouse Model of Wound Healing
title_sort ca alginate pegma hydrogels for in situ delivery of tgf β neutralizing antibodies in a mouse model of wound healing
topic hydrogel
wound healing
Ca-alginate
poly(ethylene glycol) methyl ether methacrylate
1D11
TGF-β
url https://www.mdpi.com/2076-3417/11/3/1164
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