How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/105819 https://doi.org/10.3390/biom10050675 |
Resumo: | Currently, insulin can only be administered through the subcutaneous route. Due to the flaws associated with this route, it is of interest to orally deliver this drug. However, insulin delivered orally has several barriers to overcome as it is degraded by the stomach's low pH, enzymatic content, and poor absorption in the gastrointestinal tract. Polymers with marine source like chitosan are commonly used in nanotechnology and drug delivery due to their biocompatibility and special features. This work focuses on the preparation and characterization of mucoadhesive insulin-loaded polymeric nanoparticles. Results showed a suitable mean size for oral administration (<600 nm by dynamic laser scattering), spherical shape, encapsulation efficiency (59.8%), and high recovery yield (80.6%). Circular dichroism spectroscopy demonstrated that protein retained its secondary structure after encapsulation. Moreover, the mucoadhesive potential of the nanoparticles was assessed in silico and the results, corroborated with ex-vivo experiments, showed that using chitosan strongly increases mucoadhesion. Besides, in vitro and in vivo safety assessment of the final formulation were performed, showing no toxicity. Lastly, the insulin-loaded nanoparticles were effective in reducing diabetic rats' glycemia. Overall, the coating of insulin-loaded nanoparticles with chitosan represents a potentially safe and promising approach to protect insulin and enhance peroral delivery. |
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How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Modelsmarine-derived biomoleculesdiabetes mellitusinsulinmucoadhesionnanoparticleoral deliveryAdhesivesAdministration, OralAnimalsCaco-2 CellsChitosanHumansInsulinMaleMouth MucosaNanoparticlesOral Mucosal AbsorptionRatsRats, WistarCell AdhesionCurrently, insulin can only be administered through the subcutaneous route. Due to the flaws associated with this route, it is of interest to orally deliver this drug. However, insulin delivered orally has several barriers to overcome as it is degraded by the stomach's low pH, enzymatic content, and poor absorption in the gastrointestinal tract. Polymers with marine source like chitosan are commonly used in nanotechnology and drug delivery due to their biocompatibility and special features. This work focuses on the preparation and characterization of mucoadhesive insulin-loaded polymeric nanoparticles. Results showed a suitable mean size for oral administration (<600 nm by dynamic laser scattering), spherical shape, encapsulation efficiency (59.8%), and high recovery yield (80.6%). Circular dichroism spectroscopy demonstrated that protein retained its secondary structure after encapsulation. Moreover, the mucoadhesive potential of the nanoparticles was assessed in silico and the results, corroborated with ex-vivo experiments, showed that using chitosan strongly increases mucoadhesion. Besides, in vitro and in vivo safety assessment of the final formulation were performed, showing no toxicity. Lastly, the insulin-loaded nanoparticles were effective in reducing diabetic rats' glycemia. Overall, the coating of insulin-loaded nanoparticles with chitosan represents a potentially safe and promising approach to protect insulin and enhance peroral delivery.MDPI2020-04-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/105819http://hdl.handle.net/10316/105819https://doi.org/10.3390/biom10050675eng2218-273XAmaral, MarianaMartins, Ana SofiaCatarino, JoséFaísca, PedroKumar, PradeepPinto, João F.Pinto, RuiCorreia, IsabelAscensão, LiaAfonso, Ricardo A.Gaspar, M. ManuelaCharmier, Adília J.Figueiredo, Isabel VitóriaReis, Catarina Pintoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-03-09T21:31:12Zoai:estudogeral.uc.pt:10316/105819Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:22:19.150426Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models |
title |
How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models |
spellingShingle |
How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models Amaral, Mariana marine-derived biomolecules diabetes mellitus insulin mucoadhesion nanoparticle oral delivery Adhesives Administration, Oral Animals Caco-2 Cells Chitosan Humans Insulin Male Mouth Mucosa Nanoparticles Oral Mucosal Absorption Rats Rats, Wistar Cell Adhesion |
title_short |
How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models |
title_full |
How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models |
title_fullStr |
How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models |
title_full_unstemmed |
How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models |
title_sort |
How Can Biomolecules Improve Mucoadhesion of Oral Insulin? A Comprehensive Insight using Ex-Vivo, In Silico, and In Vivo Models |
author |
Amaral, Mariana |
author_facet |
Amaral, Mariana Martins, Ana Sofia Catarino, José Faísca, Pedro Kumar, Pradeep Pinto, João F. Pinto, Rui Correia, Isabel Ascensão, Lia Afonso, Ricardo A. Gaspar, M. Manuela Charmier, Adília J. Figueiredo, Isabel Vitória Reis, Catarina Pinto |
author_role |
author |
author2 |
Martins, Ana Sofia Catarino, José Faísca, Pedro Kumar, Pradeep Pinto, João F. Pinto, Rui Correia, Isabel Ascensão, Lia Afonso, Ricardo A. Gaspar, M. Manuela Charmier, Adília J. Figueiredo, Isabel Vitória Reis, Catarina Pinto |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Amaral, Mariana Martins, Ana Sofia Catarino, José Faísca, Pedro Kumar, Pradeep Pinto, João F. Pinto, Rui Correia, Isabel Ascensão, Lia Afonso, Ricardo A. Gaspar, M. Manuela Charmier, Adília J. Figueiredo, Isabel Vitória Reis, Catarina Pinto |
dc.subject.por.fl_str_mv |
marine-derived biomolecules diabetes mellitus insulin mucoadhesion nanoparticle oral delivery Adhesives Administration, Oral Animals Caco-2 Cells Chitosan Humans Insulin Male Mouth Mucosa Nanoparticles Oral Mucosal Absorption Rats Rats, Wistar Cell Adhesion |
topic |
marine-derived biomolecules diabetes mellitus insulin mucoadhesion nanoparticle oral delivery Adhesives Administration, Oral Animals Caco-2 Cells Chitosan Humans Insulin Male Mouth Mucosa Nanoparticles Oral Mucosal Absorption Rats Rats, Wistar Cell Adhesion |
description |
Currently, insulin can only be administered through the subcutaneous route. Due to the flaws associated with this route, it is of interest to orally deliver this drug. However, insulin delivered orally has several barriers to overcome as it is degraded by the stomach's low pH, enzymatic content, and poor absorption in the gastrointestinal tract. Polymers with marine source like chitosan are commonly used in nanotechnology and drug delivery due to their biocompatibility and special features. This work focuses on the preparation and characterization of mucoadhesive insulin-loaded polymeric nanoparticles. Results showed a suitable mean size for oral administration (<600 nm by dynamic laser scattering), spherical shape, encapsulation efficiency (59.8%), and high recovery yield (80.6%). Circular dichroism spectroscopy demonstrated that protein retained its secondary structure after encapsulation. Moreover, the mucoadhesive potential of the nanoparticles was assessed in silico and the results, corroborated with ex-vivo experiments, showed that using chitosan strongly increases mucoadhesion. Besides, in vitro and in vivo safety assessment of the final formulation were performed, showing no toxicity. Lastly, the insulin-loaded nanoparticles were effective in reducing diabetic rats' glycemia. Overall, the coating of insulin-loaded nanoparticles with chitosan represents a potentially safe and promising approach to protect insulin and enhance peroral delivery. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-04-27 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/105819 http://hdl.handle.net/10316/105819 https://doi.org/10.3390/biom10050675 |
url |
http://hdl.handle.net/10316/105819 https://doi.org/10.3390/biom10050675 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2218-273X |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
|
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1799134112782483456 |