Chitosan-based oral hydrogel formulations of β-galactosidase to improve enzyme supplementation therapy for lactose intolerance

β-Galactosidase supplementation plays an important role in the life of people with lactose intolerance. However, these formulations are rendered ineffective by the low pH and pepsin in the stomach and pancreatic proteases in the intestine. Therefore, it is necessary to develop oral transport systems...

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Detalles Bibliográficos
Autores: Fraile-Gutiérrez, I., Iglesias, Susana, Acosta, Niuris, Revuelta, Julia
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/348030
Acceso en línea:http://hdl.handle.net/10261/348030
Access Level:acceso abierto
Palabra clave:β-Galactosidase
Chitosan
Lactose intolerance
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spelling Chitosan-based oral hydrogel formulations of β-galactosidase to improve enzyme supplementation therapy for lactose intoleranceFraile-Gutiérrez, I.Iglesias, SusanaAcosta, NiurisRevuelta, Juliaβ-GalactosidaseChitosanLactose intoleranceβ-Galactosidase supplementation plays an important role in the life of people with lactose intolerance. However, these formulations are rendered ineffective by the low pH and pepsin in the stomach and pancreatic proteases in the intestine. Therefore, it is necessary to develop oral transport systems for carrying this enzyme in the active form up to the intestine, where the lactose digestion occurs. In this research, a new hydrogel was developed that could potentially be used for enzyme supplement therapy. In this regard, the chitosan-based β-Gal formulations described in the manuscript are an alternative long-acting preparation to the so far available preparations that allow for enzyme protection and mucosal targeting. These hydrogels were prepared from chitosan and polyethylene glycol and contained a covalently immobilized β-galactosidase from Aspergillus oryzae. The β-galactosidase in the hydrogel was protected from degradation in a gastric medium at a pH of 2.5 and retained 75 % of its original activity under subsequent intestinal conditions. In the case of a simulated gastric fluid with a pH of 1.5, a copolymer containing methacrylic acid functional groups was sufficient to protect the hybrid hydrogel from the extremely acidic pH. In addition, the surface of the hydrogel was chemically modified with thiol and amidine groups, which increased the binding to intestinal mucin by 20 % compared with the unmodified hydrogel. These results represent a promising approach for oral transport as a reservoir for β-galactosidase in the small intestine to reduce the symptoms of hypolactasia.The authors gratefully acknowledge the financial support provided by the grant IND2019/IND-17121 (Ayudas para la realizaci´on de Doc- torados Industriales 2019, Comunidad de Madrid, Spain)Peer reviewedElsevierComunidad de MadridConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420242024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/348030reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1016/j.ijbiomac.2023.127755Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3480302026-05-22T06:33:51Z
dc.title.none.fl_str_mv Chitosan-based oral hydrogel formulations of β-galactosidase to improve enzyme supplementation therapy for lactose intolerance
title Chitosan-based oral hydrogel formulations of β-galactosidase to improve enzyme supplementation therapy for lactose intolerance
spellingShingle Chitosan-based oral hydrogel formulations of β-galactosidase to improve enzyme supplementation therapy for lactose intolerance
Fraile-Gutiérrez, I.
β-Galactosidase
Chitosan
Lactose intolerance
title_short Chitosan-based oral hydrogel formulations of β-galactosidase to improve enzyme supplementation therapy for lactose intolerance
title_full Chitosan-based oral hydrogel formulations of β-galactosidase to improve enzyme supplementation therapy for lactose intolerance
title_fullStr Chitosan-based oral hydrogel formulations of β-galactosidase to improve enzyme supplementation therapy for lactose intolerance
title_full_unstemmed Chitosan-based oral hydrogel formulations of β-galactosidase to improve enzyme supplementation therapy for lactose intolerance
title_sort Chitosan-based oral hydrogel formulations of β-galactosidase to improve enzyme supplementation therapy for lactose intolerance
dc.creator.none.fl_str_mv Fraile-Gutiérrez, I.
Iglesias, Susana
Acosta, Niuris
Revuelta, Julia
author Fraile-Gutiérrez, I.
author_facet Fraile-Gutiérrez, I.
Iglesias, Susana
Acosta, Niuris
Revuelta, Julia
author_role author
author2 Iglesias, Susana
Acosta, Niuris
Revuelta, Julia
author2_role author
author
author
dc.contributor.none.fl_str_mv Comunidad de Madrid
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv β-Galactosidase
Chitosan
Lactose intolerance
topic β-Galactosidase
Chitosan
Lactose intolerance
description β-Galactosidase supplementation plays an important role in the life of people with lactose intolerance. However, these formulations are rendered ineffective by the low pH and pepsin in the stomach and pancreatic proteases in the intestine. Therefore, it is necessary to develop oral transport systems for carrying this enzyme in the active form up to the intestine, where the lactose digestion occurs. In this research, a new hydrogel was developed that could potentially be used for enzyme supplement therapy. In this regard, the chitosan-based β-Gal formulations described in the manuscript are an alternative long-acting preparation to the so far available preparations that allow for enzyme protection and mucosal targeting. These hydrogels were prepared from chitosan and polyethylene glycol and contained a covalently immobilized β-galactosidase from Aspergillus oryzae. The β-galactosidase in the hydrogel was protected from degradation in a gastric medium at a pH of 2.5 and retained 75 % of its original activity under subsequent intestinal conditions. In the case of a simulated gastric fluid with a pH of 1.5, a copolymer containing methacrylic acid functional groups was sufficient to protect the hybrid hydrogel from the extremely acidic pH. In addition, the surface of the hydrogel was chemically modified with thiol and amidine groups, which increased the binding to intestinal mucin by 20 % compared with the unmodified hydrogel. These results represent a promising approach for oral transport as a reservoir for β-galactosidase in the small intestine to reduce the symptoms of hypolactasia.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/348030
url http://hdl.handle.net/10261/348030
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1016/j.ijbiomac.2023.127755
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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