PEGylated versus non-PEGylated pH-sensitive liposomes: new insights from a comparative antitumor activity study
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.3390/pharmaceutics14020272 http://hdl.handle.net/1843/60460 https://orcid.org/0000-0003-2594-9581 https://orcid.org/0000-0002-2457-2156 https://orcid.org/0000-0001-8812-3811 https://orcid.org/0000-0002-9521-5236 https://orcid.org/0000-0003-0463-8717 https://orcid.org/0000-0002-5650-6743 |
Resumo: | PEGylated liposomes are largely studied as long-circulating drug delivery systems. Nevertheless, the addition of PEG can result in reduced interactions between liposomes and cells, hindering liposomal internalization into target cells. The presence of PEG on the surface of pH-sensitive liposomes is not advantageous in terms of biodistribution and tumor uptake, raising the question of whether the indiscriminate use of PEG benefits the formulation. In this study, two doxorubicin-loaded pH-sensitive liposomal formulations, PEGylated (Lip2000-DOX) or non-PEGylated (Lip-DOX), were prepared and characterized. Overall, the PEGylated and non-PEGylated liposomes showed no differences in size or morphology in Cryo-TEM image analysis. Specifically, DLS analysis showed a mean diameter of 140 nm, PDI lower than 0.2, and zeta potential close to neutrality. Both formulations showed an EP higher than 90%. With respect to drug delivery, Lip-DOX had better cellular uptake than Lip2000-DOX, suggesting that the presence of PEG reduced the amount of intracellular DOX accumulation. The antitumor activities of free-DOX and both liposomal formulations were evaluated in 4T1 breast tumor-bearing BALB/c mice. The results showed that Lip-DOX was more effective in controlling tumor growth than other groups, inhibiting tumor growth by 60.4%. Histological lung analysis confirmed that none of the animals in the Lip-DOX group had metastatic foci. These results support that pH-sensitive liposomes have interesting antitumor properties and may produce important outcomes without PEG. |
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2023-11-01T21:51:51Z2023-11-01T21:51:51Z2022142https://doi.org/10.3390/pharmaceutics140202721999-4923http://hdl.handle.net/1843/60460https://orcid.org/0000-0003-2594-9581https://orcid.org/0000-0002-2457-2156https://orcid.org/0000-0001-8812-3811https://orcid.org/0000-0002-9521-5236https://orcid.org/0000-0003-0463-8717https://orcid.org/0000-0002-5650-6743PEGylated liposomes are largely studied as long-circulating drug delivery systems. Nevertheless, the addition of PEG can result in reduced interactions between liposomes and cells, hindering liposomal internalization into target cells. The presence of PEG on the surface of pH-sensitive liposomes is not advantageous in terms of biodistribution and tumor uptake, raising the question of whether the indiscriminate use of PEG benefits the formulation. In this study, two doxorubicin-loaded pH-sensitive liposomal formulations, PEGylated (Lip2000-DOX) or non-PEGylated (Lip-DOX), were prepared and characterized. Overall, the PEGylated and non-PEGylated liposomes showed no differences in size or morphology in Cryo-TEM image analysis. Specifically, DLS analysis showed a mean diameter of 140 nm, PDI lower than 0.2, and zeta potential close to neutrality. Both formulations showed an EP higher than 90%. With respect to drug delivery, Lip-DOX had better cellular uptake than Lip2000-DOX, suggesting that the presence of PEG reduced the amount of intracellular DOX accumulation. The antitumor activities of free-DOX and both liposomal formulations were evaluated in 4T1 breast tumor-bearing BALB/c mice. The results showed that Lip-DOX was more effective in controlling tumor growth than other groups, inhibiting tumor growth by 60.4%. Histological lung analysis confirmed that none of the animals in the Lip-DOX group had metastatic foci. These results support that pH-sensitive liposomes have interesting antitumor properties and may produce important outcomes without PEG.Os lipossomas PEGuilados são amplamente estudados como sistemas de administração de medicamentos de longa circulação. No entanto, a adição de PEG pode resultar na redução das interações entre lipossomas e células, dificultando a internalização lipossomal nas células alvo. A presença de PEG na superfície de lipossomas sensíveis ao pH não é vantajosa em termos de biodistribuição e absorção tumoral, levantando a questão se o uso indiscriminado de PEG beneficia a formulação. Neste estudo, duas formulações lipossomais sensíveis ao pH carregadas de doxorrubicina, PEGuiladas (Lip2000-DOX) ou não PEGuiladas (Lip-DOX), foram preparadas e caracterizadas. No geral, os lipossomas PEGuilados e não PEGuilados não mostraram diferenças no tamanho ou morfologia na análise de imagens Cryo-TEM. Especificamente, a análise DLS mostrou diâmetro médio de 140 nm, PDI inferior a 0,2 e potencial zeta próximo da neutralidade. Ambas as formulações apresentaram EP superior a 90%. No que diz respeito à administração do medicamento, o Lip-DOX apresentou melhor captação celular que o Lip2000-DOX, sugerindo que a presença de PEG reduziu a quantidade de acúmulo intracelular de DOX. As atividades antitumorais da DOX livre e de ambas as formulações lipossomais foram avaliadas em camundongos BALB/c portadores de tumor de mama 4T1. Os resultados mostraram que Lip-DOX foi mais eficaz no controle do crescimento tumoral do que outros grupos, inibindo o crescimento tumoral em 60,4%. A análise histológica do pulmão confirmou que nenhum dos animais do grupo Lip-DOX apresentava focos metastáticos. Estes resultados apoiam que os lipossomas sensíveis ao pH têm propriedades antitumorais interessantes e podem produzir resultados importantes sem PEG.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisporUniversidade Federal de Minas GeraisUFMGBrasilFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICASFAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOSICB - DEPARTAMENTO DE PATOLOGIAPharmaceuticsLipossomosAntineoplásicosPolietilenoglicóisNeoplasiasDoxorrubicinaLiposomesPolyethylene glycolAntitumor activityPEGylated liposomesDoxorubicinPEGylated versus non-PEGylated pH-sensitive liposomes: new insights from a comparative antitumor activity studyLipossomas sensíveis ao pH PEGuilados versus não PEGuilados: novos insights de um estudo comparativo de atividade antitumoralinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.mdpi.com/1999-4923/14/2/272Shirleide Santos NunesMônica Cristina OliveiraAndré Luís Branco de BarrosJuliana de Oliveira SilvaRenata Salgado FernandesSued Eustaquio Mendes MirandaElaine Amaral LeiteMarcelo Alexandre de FariasRodrigo Villares PortugalGeovanni Dantas CassaliDanyelle M. Townsendapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/60460/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALPEGylated versus non-PEGylated pH-sensitive liposomes_ new insights from a comparative antitumor activity study.pdfPEGylated versus non-PEGylated pH-sensitive liposomes_ new insights from a comparative antitumor activity study.pdfapplication/pdf1278391https://repositorio.ufmg.br/bitstream/1843/60460/2/PEGylated%20versus%20non-PEGylated%20pH-sensitive%20liposomes_%20new%20insights%20from%20a%20comparative%20antitumor%20activity%20study.pdf128f1c6f05c37d207def4e20284741fcMD521843/604602023-11-01 18:51:52.036oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-11-01T21:51:52Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
PEGylated versus non-PEGylated pH-sensitive liposomes: new insights from a comparative antitumor activity study |
dc.title.alternative.pt_BR.fl_str_mv |
Lipossomas sensíveis ao pH PEGuilados versus não PEGuilados: novos insights de um estudo comparativo de atividade antitumoral |
title |
PEGylated versus non-PEGylated pH-sensitive liposomes: new insights from a comparative antitumor activity study |
spellingShingle |
PEGylated versus non-PEGylated pH-sensitive liposomes: new insights from a comparative antitumor activity study Shirleide Santos Nunes Liposomes Polyethylene glycol Antitumor activity PEGylated liposomes Doxorubicin Lipossomos Antineoplásicos Polietilenoglicóis Neoplasias Doxorrubicina |
title_short |
PEGylated versus non-PEGylated pH-sensitive liposomes: new insights from a comparative antitumor activity study |
title_full |
PEGylated versus non-PEGylated pH-sensitive liposomes: new insights from a comparative antitumor activity study |
title_fullStr |
PEGylated versus non-PEGylated pH-sensitive liposomes: new insights from a comparative antitumor activity study |
title_full_unstemmed |
PEGylated versus non-PEGylated pH-sensitive liposomes: new insights from a comparative antitumor activity study |
title_sort |
PEGylated versus non-PEGylated pH-sensitive liposomes: new insights from a comparative antitumor activity study |
author |
Shirleide Santos Nunes |
author_facet |
Shirleide Santos Nunes Mônica Cristina Oliveira André Luís Branco de Barros Juliana de Oliveira Silva Renata Salgado Fernandes Sued Eustaquio Mendes Miranda Elaine Amaral Leite Marcelo Alexandre de Farias Rodrigo Villares Portugal Geovanni Dantas Cassali Danyelle M. Townsend |
author_role |
author |
author2 |
Mônica Cristina Oliveira André Luís Branco de Barros Juliana de Oliveira Silva Renata Salgado Fernandes Sued Eustaquio Mendes Miranda Elaine Amaral Leite Marcelo Alexandre de Farias Rodrigo Villares Portugal Geovanni Dantas Cassali Danyelle M. Townsend |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Shirleide Santos Nunes Mônica Cristina Oliveira André Luís Branco de Barros Juliana de Oliveira Silva Renata Salgado Fernandes Sued Eustaquio Mendes Miranda Elaine Amaral Leite Marcelo Alexandre de Farias Rodrigo Villares Portugal Geovanni Dantas Cassali Danyelle M. Townsend |
dc.subject.por.fl_str_mv |
Liposomes Polyethylene glycol Antitumor activity PEGylated liposomes Doxorubicin |
topic |
Liposomes Polyethylene glycol Antitumor activity PEGylated liposomes Doxorubicin Lipossomos Antineoplásicos Polietilenoglicóis Neoplasias Doxorrubicina |
dc.subject.other.pt_BR.fl_str_mv |
Lipossomos Antineoplásicos Polietilenoglicóis Neoplasias Doxorrubicina |
description |
PEGylated liposomes are largely studied as long-circulating drug delivery systems. Nevertheless, the addition of PEG can result in reduced interactions between liposomes and cells, hindering liposomal internalization into target cells. The presence of PEG on the surface of pH-sensitive liposomes is not advantageous in terms of biodistribution and tumor uptake, raising the question of whether the indiscriminate use of PEG benefits the formulation. In this study, two doxorubicin-loaded pH-sensitive liposomal formulations, PEGylated (Lip2000-DOX) or non-PEGylated (Lip-DOX), were prepared and characterized. Overall, the PEGylated and non-PEGylated liposomes showed no differences in size or morphology in Cryo-TEM image analysis. Specifically, DLS analysis showed a mean diameter of 140 nm, PDI lower than 0.2, and zeta potential close to neutrality. Both formulations showed an EP higher than 90%. With respect to drug delivery, Lip-DOX had better cellular uptake than Lip2000-DOX, suggesting that the presence of PEG reduced the amount of intracellular DOX accumulation. The antitumor activities of free-DOX and both liposomal formulations were evaluated in 4T1 breast tumor-bearing BALB/c mice. The results showed that Lip-DOX was more effective in controlling tumor growth than other groups, inhibiting tumor growth by 60.4%. Histological lung analysis confirmed that none of the animals in the Lip-DOX group had metastatic foci. These results support that pH-sensitive liposomes have interesting antitumor properties and may produce important outcomes without PEG. |
publishDate |
2022 |
dc.date.issued.fl_str_mv |
2022 |
dc.date.accessioned.fl_str_mv |
2023-11-01T21:51:51Z |
dc.date.available.fl_str_mv |
2023-11-01T21:51:51Z |
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/1843/60460 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.3390/pharmaceutics14020272 |
dc.identifier.issn.pt_BR.fl_str_mv |
1999-4923 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0003-2594-9581 https://orcid.org/0000-0002-2457-2156 https://orcid.org/0000-0001-8812-3811 https://orcid.org/0000-0002-9521-5236 https://orcid.org/0000-0003-0463-8717 https://orcid.org/0000-0002-5650-6743 |
url |
https://doi.org/10.3390/pharmaceutics14020272 http://hdl.handle.net/1843/60460 https://orcid.org/0000-0003-2594-9581 https://orcid.org/0000-0002-2457-2156 https://orcid.org/0000-0001-8812-3811 https://orcid.org/0000-0002-9521-5236 https://orcid.org/0000-0003-0463-8717 https://orcid.org/0000-0002-5650-6743 |
identifier_str_mv |
1999-4923 |
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por |
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por |
dc.relation.ispartof.pt_BR.fl_str_mv |
Pharmaceutics |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Universidade Federal de Minas Gerais |
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UFMG |
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Brasil |
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FAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS FAR - DEPARTAMENTO DE PRODUTOS FARMACÊUTICOS ICB - DEPARTAMENTO DE PATOLOGIA |
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Universidade Federal de Minas Gerais |
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reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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