Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlys
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/1822/77190 |
Resumo: | An increase in bacterial resistance to systemic antibiotics has sparked interest into alternative antimicrobial compounds as well as methods for effective local, non-invasive drug delivery. Topical treatments, however, may be hindered by the presence of biological barriers, such as the tympanic membrane in the case of otitis media. Herein, the transtympanic permeation ability of liposomes loaded with the pneumococcal endolysin MSlys and of free MSlys was evaluated ex vivo. MSlys loaded in PEGylated liposomes showed an increased permeation across human tympanic membranes, as compared to its free form, being able to reduce the pneumococcal cell load after 2 h of permeation. However, antipneumococcal activity was no longer detected after 4 h of permeation and hydrolysis of the endolysin was observed after an extended incubation time ( 48 h). This work provides a first assessment of a successful, non-invasive delivery method for endolysins across an intact tympanic membrane. Findings have implications for non-systemic, local treatment of otitis media. |
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Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlysdrug deliveryendolysinliposomeMSlystranstympanicStreptococcus pneumoniaeScience & TechnologyAn increase in bacterial resistance to systemic antibiotics has sparked interest into alternative antimicrobial compounds as well as methods for effective local, non-invasive drug delivery. Topical treatments, however, may be hindered by the presence of biological barriers, such as the tympanic membrane in the case of otitis media. Herein, the transtympanic permeation ability of liposomes loaded with the pneumococcal endolysin MSlys and of free MSlys was evaluated ex vivo. MSlys loaded in PEGylated liposomes showed an increased permeation across human tympanic membranes, as compared to its free form, being able to reduce the pneumococcal cell load after 2 h of permeation. However, antipneumococcal activity was no longer detected after 4 h of permeation and hydrolysis of the endolysin was observed after an extended incubation time ( 48 h). This work provides a first assessment of a successful, non-invasive delivery method for endolysins across an intact tympanic membrane. Findings have implications for non-systemic, local treatment of otitis media.This study was partially supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2020 unit. MDS acknowledges support from the FCT doctoral fellowship, reference SFRH/BD/128825/2017 and COVID/BD/152363/2022. SS acknowledges funding by FCT, through the individual scientific employment program contract (2020.03171.CEECIND). AKR acknowledges funding to support this project from the Wyss Institute for Biologically Inspired Engineering at Harvard University and from NIH NIDCD K08-DC018575info:eu-repo/semantics/publishedVersionElsevierUniversidade do MinhoSilva, Maria DanielaRay, KaelinGama, F. M.Remenschneider, Aaron K.Sillankorva, Sanna2022-05-252022-05-25T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/1822/77190engSilva, Maria Daniela; Ray, Kaelin; Gama, F. M.; Remenschneider, Aaron K.; Sillankorva, Sanna, Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlys. International Journal of Pharmaceutics, 620(121752), 20220378-517310.1016/j.ijpharm.2022.12175235439573121752http://www.elsevier.com/locate/issn/03785173info: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:RCAAP2023-07-21T11:55:54Zoai:repositorium.sdum.uminho.pt:1822/77190Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:45:27.078288Repositório 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 |
Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlys |
title |
Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlys |
spellingShingle |
Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlys Silva, Maria Daniela drug delivery endolysin liposome MSlys transtympanic Streptococcus pneumoniae Science & Technology |
title_short |
Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlys |
title_full |
Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlys |
title_fullStr |
Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlys |
title_full_unstemmed |
Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlys |
title_sort |
Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlys |
author |
Silva, Maria Daniela |
author_facet |
Silva, Maria Daniela Ray, Kaelin Gama, F. M. Remenschneider, Aaron K. Sillankorva, Sanna |
author_role |
author |
author2 |
Ray, Kaelin Gama, F. M. Remenschneider, Aaron K. Sillankorva, Sanna |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Silva, Maria Daniela Ray, Kaelin Gama, F. M. Remenschneider, Aaron K. Sillankorva, Sanna |
dc.subject.por.fl_str_mv |
drug delivery endolysin liposome MSlys transtympanic Streptococcus pneumoniae Science & Technology |
topic |
drug delivery endolysin liposome MSlys transtympanic Streptococcus pneumoniae Science & Technology |
description |
An increase in bacterial resistance to systemic antibiotics has sparked interest into alternative antimicrobial compounds as well as methods for effective local, non-invasive drug delivery. Topical treatments, however, may be hindered by the presence of biological barriers, such as the tympanic membrane in the case of otitis media. Herein, the transtympanic permeation ability of liposomes loaded with the pneumococcal endolysin MSlys and of free MSlys was evaluated ex vivo. MSlys loaded in PEGylated liposomes showed an increased permeation across human tympanic membranes, as compared to its free form, being able to reduce the pneumococcal cell load after 2 h of permeation. However, antipneumococcal activity was no longer detected after 4 h of permeation and hydrolysis of the endolysin was observed after an extended incubation time ( 48 h). This work provides a first assessment of a successful, non-invasive delivery method for endolysins across an intact tympanic membrane. Findings have implications for non-systemic, local treatment of otitis media. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-05-25 2022-05-25T00:00:00Z |
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 |
https://hdl.handle.net/1822/77190 |
url |
https://hdl.handle.net/1822/77190 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Silva, Maria Daniela; Ray, Kaelin; Gama, F. M.; Remenschneider, Aaron K.; Sillankorva, Sanna, Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlys. International Journal of Pharmaceutics, 620(121752), 2022 0378-5173 10.1016/j.ijpharm.2022.121752 35439573 121752 http://www.elsevier.com/locate/issn/03785173 |
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 |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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) |
collection |
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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