Anti-EGFR liquid crystalline nanodispersions for docetaxel delivery: Formulation, characterization and cytotoxicity in cancer cells
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.colsurfa.2020.126058 http://hdl.handle.net/11449/207124 |
Resumo: | Prostate cancer is one of the most frequent neoplasms, associated with high mortality. Some factors may intensify its aggressiveness, for example, the overexpression of the epidermal growth factor receptor (EGFR) in some subtypes of prostate tumors. In this context, the inhibition of EGFR helps to fight neoplasia, with the use of the chimeric anti-EGFR monoclonal antibody, cetuximab (CTX). For cancer treatment in the metastatic stage, chemotherapy using docetaxel (DTX) is widely employed, however the drug is very liposoluble, hampering its bioavailability. In this sense, liquid crystalline systems have great potential for the delivery of DTX. Particularly, liquid crystalline nanodispersions can be used in parenteral routes, with many advantages, including the possibility of prolonged drug release, improved pharmacokinetics, allowing passive tumor accumulation by the EPR effect. Thus, the objective of this work was to develop a liquid crystalline nanodispersion (LCN) based on ethoxylated cetyl alcohol 20 and propoxylated 5 as surfactant (Procetyl®), oleic acid, DSPE-PEG-MAL (anchor for CTX binding) and soy phosphatidylcholine as oily phase and 1.5 % poloxamer dispersion in PBS buffer as an aqueous phase. The formulation was loaded with DTX and covalently functionalized with CTX to evaluate its cytotoxic potential against prostate cancer cells. The results suggested that the obtained system has a predominantly hexagonal crystalline phase, was able to be nanodispersed with low polydispersity, and presented negative zeta potential. CTX did not have its structure compromised after thiolation and was successfully covalently linked to LCN. In a prostate cancer cells, PC3, LCNs functionalized with CTX underwent greater cell uptake, resulting in greater cytotoxicity, compared to free DTX and non-functionalized DTX-loaded LCNs. Therefore, the present study reports for the first time an EGFR-targeted liquid crystal nanodispersion for selective to deliver DTX to prostate cells |
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Anti-EGFR liquid crystalline nanodispersions for docetaxel delivery: Formulation, characterization and cytotoxicity in cancer cellsCetuximabDocetaxelHexosomeLiquid crystalNanodispersionProstate cancer is one of the most frequent neoplasms, associated with high mortality. Some factors may intensify its aggressiveness, for example, the overexpression of the epidermal growth factor receptor (EGFR) in some subtypes of prostate tumors. In this context, the inhibition of EGFR helps to fight neoplasia, with the use of the chimeric anti-EGFR monoclonal antibody, cetuximab (CTX). For cancer treatment in the metastatic stage, chemotherapy using docetaxel (DTX) is widely employed, however the drug is very liposoluble, hampering its bioavailability. In this sense, liquid crystalline systems have great potential for the delivery of DTX. Particularly, liquid crystalline nanodispersions can be used in parenteral routes, with many advantages, including the possibility of prolonged drug release, improved pharmacokinetics, allowing passive tumor accumulation by the EPR effect. Thus, the objective of this work was to develop a liquid crystalline nanodispersion (LCN) based on ethoxylated cetyl alcohol 20 and propoxylated 5 as surfactant (Procetyl®), oleic acid, DSPE-PEG-MAL (anchor for CTX binding) and soy phosphatidylcholine as oily phase and 1.5 % poloxamer dispersion in PBS buffer as an aqueous phase. The formulation was loaded with DTX and covalently functionalized with CTX to evaluate its cytotoxic potential against prostate cancer cells. The results suggested that the obtained system has a predominantly hexagonal crystalline phase, was able to be nanodispersed with low polydispersity, and presented negative zeta potential. CTX did not have its structure compromised after thiolation and was successfully covalently linked to LCN. In a prostate cancer cells, PC3, LCNs functionalized with CTX underwent greater cell uptake, resulting in greater cytotoxicity, compared to free DTX and non-functionalized DTX-loaded LCNs. Therefore, the present study reports for the first time an EGFR-targeted liquid crystal nanodispersion for selective to deliver DTX to prostate cellsFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)School of Pharmaceutical Sciences of Araraquara São Paulo State University UNESP Department of Drugs and MedicinesFederal University of Ceará College of Pharmacy Dentistry and Nursing Department of PharmacyUniversity of International Integration of the Afro-Brazilian Lusophony Institute of Health SciencesSão Carlos Institute of Chemistry University of São Paulo, São CarlosSchool of Pharmaceutical Sciences of Ribeirão Preto University of São Paulo Ribeirão PretoSchool of Pharmaceutical Sciences of Araraquara São Paulo State University UNESP Department of Drugs and MedicinesCNPq: # 465687/2014-8FAPESP: #2014/50928-2Universidade Estadual Paulista (Unesp)Dentistry and NursingInstitute of Health SciencesUniversidade de São Paulo (USP)Trevizan, Lucas Noboru Fatori [UNESP]Eloy, Josimar O.Luiz, Marcela TavaresPetrilli, RaquelJunior, Sergio Luiz RamosBorges, Julio CésarMarchetti, Juliana MaldonadoChorilli, Marlus [UNESP]2021-06-25T10:49:19Z2021-06-25T10:49:19Z2021-03-20info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.colsurfa.2020.126058Colloids and Surfaces A: Physicochemical and Engineering Aspects, v. 613.1873-43590927-7757http://hdl.handle.net/11449/20712410.1016/j.colsurfa.2020.1260582-s2.0-85099263069Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengColloids and Surfaces A: Physicochemical and Engineering Aspectsinfo:eu-repo/semantics/openAccess2021-10-23T16:00:38Zoai:repositorio.unesp.br:11449/207124Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462021-10-23T16:00:38Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Anti-EGFR liquid crystalline nanodispersions for docetaxel delivery: Formulation, characterization and cytotoxicity in cancer cells |
title |
Anti-EGFR liquid crystalline nanodispersions for docetaxel delivery: Formulation, characterization and cytotoxicity in cancer cells |
spellingShingle |
Anti-EGFR liquid crystalline nanodispersions for docetaxel delivery: Formulation, characterization and cytotoxicity in cancer cells Trevizan, Lucas Noboru Fatori [UNESP] Cetuximab Docetaxel Hexosome Liquid crystal Nanodispersion |
title_short |
Anti-EGFR liquid crystalline nanodispersions for docetaxel delivery: Formulation, characterization and cytotoxicity in cancer cells |
title_full |
Anti-EGFR liquid crystalline nanodispersions for docetaxel delivery: Formulation, characterization and cytotoxicity in cancer cells |
title_fullStr |
Anti-EGFR liquid crystalline nanodispersions for docetaxel delivery: Formulation, characterization and cytotoxicity in cancer cells |
title_full_unstemmed |
Anti-EGFR liquid crystalline nanodispersions for docetaxel delivery: Formulation, characterization and cytotoxicity in cancer cells |
title_sort |
Anti-EGFR liquid crystalline nanodispersions for docetaxel delivery: Formulation, characterization and cytotoxicity in cancer cells |
author |
Trevizan, Lucas Noboru Fatori [UNESP] |
author_facet |
Trevizan, Lucas Noboru Fatori [UNESP] Eloy, Josimar O. Luiz, Marcela Tavares Petrilli, Raquel Junior, Sergio Luiz Ramos Borges, Julio César Marchetti, Juliana Maldonado Chorilli, Marlus [UNESP] |
author_role |
author |
author2 |
Eloy, Josimar O. Luiz, Marcela Tavares Petrilli, Raquel Junior, Sergio Luiz Ramos Borges, Julio César Marchetti, Juliana Maldonado Chorilli, Marlus [UNESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Dentistry and Nursing Institute of Health Sciences Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
Trevizan, Lucas Noboru Fatori [UNESP] Eloy, Josimar O. Luiz, Marcela Tavares Petrilli, Raquel Junior, Sergio Luiz Ramos Borges, Julio César Marchetti, Juliana Maldonado Chorilli, Marlus [UNESP] |
dc.subject.por.fl_str_mv |
Cetuximab Docetaxel Hexosome Liquid crystal Nanodispersion |
topic |
Cetuximab Docetaxel Hexosome Liquid crystal Nanodispersion |
description |
Prostate cancer is one of the most frequent neoplasms, associated with high mortality. Some factors may intensify its aggressiveness, for example, the overexpression of the epidermal growth factor receptor (EGFR) in some subtypes of prostate tumors. In this context, the inhibition of EGFR helps to fight neoplasia, with the use of the chimeric anti-EGFR monoclonal antibody, cetuximab (CTX). For cancer treatment in the metastatic stage, chemotherapy using docetaxel (DTX) is widely employed, however the drug is very liposoluble, hampering its bioavailability. In this sense, liquid crystalline systems have great potential for the delivery of DTX. Particularly, liquid crystalline nanodispersions can be used in parenteral routes, with many advantages, including the possibility of prolonged drug release, improved pharmacokinetics, allowing passive tumor accumulation by the EPR effect. Thus, the objective of this work was to develop a liquid crystalline nanodispersion (LCN) based on ethoxylated cetyl alcohol 20 and propoxylated 5 as surfactant (Procetyl®), oleic acid, DSPE-PEG-MAL (anchor for CTX binding) and soy phosphatidylcholine as oily phase and 1.5 % poloxamer dispersion in PBS buffer as an aqueous phase. The formulation was loaded with DTX and covalently functionalized with CTX to evaluate its cytotoxic potential against prostate cancer cells. The results suggested that the obtained system has a predominantly hexagonal crystalline phase, was able to be nanodispersed with low polydispersity, and presented negative zeta potential. CTX did not have its structure compromised after thiolation and was successfully covalently linked to LCN. In a prostate cancer cells, PC3, LCNs functionalized with CTX underwent greater cell uptake, resulting in greater cytotoxicity, compared to free DTX and non-functionalized DTX-loaded LCNs. Therefore, the present study reports for the first time an EGFR-targeted liquid crystal nanodispersion for selective to deliver DTX to prostate cells |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-06-25T10:49:19Z 2021-06-25T10:49:19Z 2021-03-20 |
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://dx.doi.org/10.1016/j.colsurfa.2020.126058 Colloids and Surfaces A: Physicochemical and Engineering Aspects, v. 613. 1873-4359 0927-7757 http://hdl.handle.net/11449/207124 10.1016/j.colsurfa.2020.126058 2-s2.0-85099263069 |
url |
http://dx.doi.org/10.1016/j.colsurfa.2020.126058 http://hdl.handle.net/11449/207124 |
identifier_str_mv |
Colloids and Surfaces A: Physicochemical and Engineering Aspects, v. 613. 1873-4359 0927-7757 10.1016/j.colsurfa.2020.126058 2-s2.0-85099263069 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Colloids and Surfaces A: Physicochemical and Engineering Aspects |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1799965473897447424 |