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/10451/51634 |
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 deliveryCurrently, 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.Supported in part by UID/DTP/04138/2019 from FCT, Portugal and DREAMS (ULHT). SEM analysis was funded by FCT/MCTES for the financial support to CESAM (UIDP/50017/2020+UIDB/50017/2020), through national funds. Acknowledgments: The authors are grateful to the Carla Vânia (iMedUlisboa) for her collaboration in HPLC analysis and Joana Moreira (ECTS-ULHT) for her collaboration in conducting some experiments.MDPIRepositório da Universidade de LisboaAmaral, MarianaMartins, Ana SofiaCatarino, JoséFaísca, PedroKumar, PradeepPinto, João F.Pinto, RuiCorreia, IsabelAscensão, LiaAfonso, Ricardo A.Gaspar, CatarinaCharmier, Adília J.Figueiredo, Isabel VitóriaReis, Catarina Pinto2022-03-07T16:26:16Z2020-04-272022-02-21T09:24:42Z2020-04-27T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/51634engAmaral M, Martins AS, Catarino J, Faísca P, Kumar P, Pinto JF, et al. How can biomolecules improve mucoadhesion of oral insulin? A comprehensive insight using ex-vivo, in silico, and in vivo models. Biomolecules [Internet]. 2020;10(5):675. Disponível em: https://www.mdpi.com/2218-273X/10/5/6752218-273Xcv-prod-1634277doi.org/10.3390/biom100506752-s2.0-85083970308info: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:RCAAP2023-11-08T16:56:06Zoai:repositorio.ul.pt:10451/51634Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:02:42.362512Repositório 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 |
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, Catarina 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, Catarina 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.none.fl_str_mv |
Repositório da Universidade de Lisboa |
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, Catarina 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 |
topic |
Marine-derived biomolecules Diabetes mellitus Insulin Mucoadhesion Nanoparticle Oral delivery |
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 2020-04-27T00:00:00Z 2022-03-07T16:26:16Z 2022-02-21T09:24:42Z |
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/10451/51634 |
url |
http://hdl.handle.net/10451/51634 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Amaral M, Martins AS, Catarino J, Faísca P, Kumar P, Pinto JF, et al. How can biomolecules improve mucoadhesion of oral insulin? A comprehensive insight using ex-vivo, in silico, and in vivo models. Biomolecules [Internet]. 2020;10(5):675. Disponível em: https://www.mdpi.com/2218-273X/10/5/675 2218-273X cv-prod-1634277 doi.org/10.3390/biom10050675 2-s2.0-85083970308 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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