A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer

Paclitaxel (PTX), a chemotherapy agent widely used to treat lung cancer, is characterised by high toxicity, low bioavailability and the need to use of excipients with serious side effects that limit its use. Paclitaxel encapsulation into nanoparticles (NPs) generates drug pharmacokinetic and pharmac...

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Autores: Jiménez López, Julia, El Hammadi, Mazen M., Ortiz, Raul, Cayero Otero, María Dolores, Cabeza, Laura, Perazzoli, Gloria, Martín Banderas, Lucía, Baeyens, Jose M., Prados, Jose, Melguizo, Consolación
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/165960
Acceso en línea:https://hdl.handle.net/11441/165960
https://doi.org/10.1016/j.phrs.2019.01.013
Access Level:acceso abierto
Palabra clave:Paclitaxel
PLGA
Lung cáncer
Drug resistance
Neurotoxicity
Biodistribution
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spelling A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancerJiménez López, JuliaEl Hammadi, Mazen M.Ortiz, RaulCayero Otero, María DoloresCabeza, LauraPerazzoli, GloriaMartín Banderas, LucíaBaeyens, Jose M.Prados, JoseMelguizo, ConsolaciónPaclitaxelPLGALung cáncerDrug resistanceNeurotoxicityBiodistributionPaclitaxel (PTX), a chemotherapy agent widely used to treat lung cancer, is characterised by high toxicity, low bioavailability and the need to use of excipients with serious side effects that limit its use. Paclitaxel encapsulation into nanoparticles (NPs) generates drug pharmacokinetic and pharmacodynamic advantages compared to free PTX. In this context, a NP carrier formed from a copolymer of lactic acid and glycolic acid (PLGA) has demonstrated high biocompatibility and low toxicity and therefore being approved by FDA to be used in humans. We synthesised a new PLGA NP and loaded it with PTX to improve drug efficacy and reduce side effects. This nanoformulation showed biocompatibility and no toxicity to human immune system. These NPs favor the intracellular uptake of PTX and enhance its antitumor effect in human and murine lung cancer cells, with up to 3.6-fold reductions in the PTX’s IC50. Although PLGA NPs did not show any inhibitory capacity against P-glycoprotein, they increased the antitumor activity of PTX in cancer stem cells. Treatment with PLGA-PTX NPs increased apoptosis and significantly reduced the volume of the tumorspheres derived from A549 and LL2 cells by up to 36% and 46.5%, respectively. Biodistribution studies with PLGA-PTX NPs revealed an increase in drug circulation time, as well as a greater accumulation in lung and brain tissues compared to free PTX. Low levels of PTX were detected in the dorsal root ganglion with PLGA-PTX NPs, which could exert a protective effect against peripheral neuropathy. In vivo treatment with PLGA-PTX NPs showed a greater decrease in tumor volume (44.6%) in immunocompetent mice compared to free PTX (24.4%) and without increasing the toxicity of the drug. These promising results suggest that developed nanosystem provide a potential strategy for improving the chemotherapeutic effect and reducing the side effects of PTX.ElsevierFarmacia y Tecnología FarmacéuticaJunta de AndalucíaUniversidad de Granada2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/165960https://doi.org/10.1016/j.phrs.2019.01.013reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésPharmacological Research, 141, 451-465.Jiménez López, J., El Hammadi, M.M.,...,Melguizo, C. (2024). Dataset from A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer. Pharmacol Res 2019 (v.0). idUS (Depósito de Investigación de la Universidad de Sevilla). https://doi.org/10.12795/11441/165979.P11-CTS-7649PI-0476-2016PP2015-13PI-0102-2017PI-0038-2014https://dx.doi.org/10.1016/j.phrs.2019.01.013info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1659602026-06-17T12:51:07Z
dc.title.none.fl_str_mv A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer
title A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer
spellingShingle A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer
Jiménez López, Julia
Paclitaxel
PLGA
Lung cáncer
Drug resistance
Neurotoxicity
Biodistribution
title_short A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer
title_full A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer
title_fullStr A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer
title_full_unstemmed A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer
title_sort A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer
dc.creator.none.fl_str_mv Jiménez López, Julia
El Hammadi, Mazen M.
Ortiz, Raul
Cayero Otero, María Dolores
Cabeza, Laura
Perazzoli, Gloria
Martín Banderas, Lucía
Baeyens, Jose M.
Prados, Jose
Melguizo, Consolación
author Jiménez López, Julia
author_facet Jiménez López, Julia
El Hammadi, Mazen M.
Ortiz, Raul
Cayero Otero, María Dolores
Cabeza, Laura
Perazzoli, Gloria
Martín Banderas, Lucía
Baeyens, Jose M.
Prados, Jose
Melguizo, Consolación
author_role author
author2 El Hammadi, Mazen M.
Ortiz, Raul
Cayero Otero, María Dolores
Cabeza, Laura
Perazzoli, Gloria
Martín Banderas, Lucía
Baeyens, Jose M.
Prados, Jose
Melguizo, Consolación
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Farmacia y Tecnología Farmacéutica
Junta de Andalucía
Universidad de Granada
dc.subject.none.fl_str_mv Paclitaxel
PLGA
Lung cáncer
Drug resistance
Neurotoxicity
Biodistribution
topic Paclitaxel
PLGA
Lung cáncer
Drug resistance
Neurotoxicity
Biodistribution
description Paclitaxel (PTX), a chemotherapy agent widely used to treat lung cancer, is characterised by high toxicity, low bioavailability and the need to use of excipients with serious side effects that limit its use. Paclitaxel encapsulation into nanoparticles (NPs) generates drug pharmacokinetic and pharmacodynamic advantages compared to free PTX. In this context, a NP carrier formed from a copolymer of lactic acid and glycolic acid (PLGA) has demonstrated high biocompatibility and low toxicity and therefore being approved by FDA to be used in humans. We synthesised a new PLGA NP and loaded it with PTX to improve drug efficacy and reduce side effects. This nanoformulation showed biocompatibility and no toxicity to human immune system. These NPs favor the intracellular uptake of PTX and enhance its antitumor effect in human and murine lung cancer cells, with up to 3.6-fold reductions in the PTX’s IC50. Although PLGA NPs did not show any inhibitory capacity against P-glycoprotein, they increased the antitumor activity of PTX in cancer stem cells. Treatment with PLGA-PTX NPs increased apoptosis and significantly reduced the volume of the tumorspheres derived from A549 and LL2 cells by up to 36% and 46.5%, respectively. Biodistribution studies with PLGA-PTX NPs revealed an increase in drug circulation time, as well as a greater accumulation in lung and brain tissues compared to free PTX. Low levels of PTX were detected in the dorsal root ganglion with PLGA-PTX NPs, which could exert a protective effect against peripheral neuropathy. In vivo treatment with PLGA-PTX NPs showed a greater decrease in tumor volume (44.6%) in immunocompetent mice compared to free PTX (24.4%) and without increasing the toxicity of the drug. These promising results suggest that developed nanosystem provide a potential strategy for improving the chemotherapeutic effect and reducing the side effects of PTX.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/165960
https://doi.org/10.1016/j.phrs.2019.01.013
url https://hdl.handle.net/11441/165960
https://doi.org/10.1016/j.phrs.2019.01.013
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Pharmacological Research, 141, 451-465.
Jiménez López, J., El Hammadi, M.M.,...,Melguizo, C. (2024). Dataset from A novel nanoformulation of PLGA with high non-ionic surfactant content improves in vitro and in vivo PTX activity against lung cancer. Pharmacol Res 2019 (v.0). idUS (Depósito de Investigación de la Universidad de Sevilla). https://doi.org/10.12795/11441/165979.
P11-CTS-7649
PI-0476-2016
PP2015-13
PI-0102-2017
PI-0038-2014
https://dx.doi.org/10.1016/j.phrs.2019.01.013
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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