Ex vivo transtympanic permeation of the liposome encapsulated S. pneumoniae endolysin MSlys

Detalhes bibliográficos
Autor(a) principal: Silva, Maria Daniela
Data de Publicação: 2022
Outros Autores: Ray, Kaelin, Gama, F. M., Remenschneider, Aaron K., Sillankorva, Sanna
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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spelling 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
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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
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