Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate delivery

Detalhes bibliográficos
Autor(a) principal: Brandt, João Victor [UNESP]
Data de Publicação: 2019
Outros Autores: Piazza, Rodolfo Debone [UNESP], dos Santos, Caio Carvalho [UNESP], Vega-Chacón, Jaime [UNESP], Amantéa, Bruno Estevam [UNESP], Pinto, Gabriel Cardoso [UNESP], Magnani, Marina [UNESP], Piva, Henrique Luís, Tedesco, Antonio Claudio, Primo, Fernando Lucas [UNESP], Jafelicci, Miguel [UNESP], Marques, Rodrigo Fernando Costa [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.colsurfb.2019.02.008
http://hdl.handle.net/11449/188704
Resumo: Hydrophobic drugs, such as methotrexate, are not easily delivered into the human body. Therefore, the use of amphiphilic nanoplatforms to the transport of these drugs through the bloodstream is a challenge. While the hydrophobic region interacts with the drug, the hydrophilic outer layer enhances its bioavailability and circulation time. Poly (ethylene glycol)-block-poly(ε-caprolactone) PEG-b-PCL micelles are biodegradable and biocompatible, allowing its use as a nanocarrier for drug delivery systems. The stealth property of PEG that composes the outer layer of nanoplatforms, makes the micelle unperceivable to phagocytic cells, increasing the circulation time in the human body. In addition, folic acid functionalization enables micelle selectively targeting to cancer cells, improving treatment efficiency and reducing side effects. In this work, PEG-b-PCL copolymer was synthesized by ring opening polymerization (ROP) of the ε-caprolactone with Poly(ethylene glycol) as a macroinitiator and tin(II) 2-ethyl hexanoate as a catalyst. Functionalization of such micelles with folic acid occurred through the modification of the PEG terminal group. The surface modification of the copolymer micelles resulted in higher critical micellar concentration (CMC), increasing approximately 100 times. The synthesis of the copolymers resulted in molecular weight around 3000 g mol −1 with low polydispersity. The polymer micelles have a hydrodynamic diameter in the range of 100–200 nm and the functionalized sample doesn't show aggregation in the considered pH range. High incorporation efficiency was obtained with a minimum percentage of 85%. The drug release profile and linearization from the Peppas model confirmed the interaction of methotrexate with the hydrophobic segment of the copolymer and its release mechanism by relaxation and/or degradation of the chains, making PEG-b-PCL micelles suitable candidates for hydrophobic drug delivery systems.
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spelling Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate deliveryCopolymer micellesMethotrexatePEG-b-PCLTargeted drug deliveryHydrophobic drugs, such as methotrexate, are not easily delivered into the human body. Therefore, the use of amphiphilic nanoplatforms to the transport of these drugs through the bloodstream is a challenge. While the hydrophobic region interacts with the drug, the hydrophilic outer layer enhances its bioavailability and circulation time. Poly (ethylene glycol)-block-poly(ε-caprolactone) PEG-b-PCL micelles are biodegradable and biocompatible, allowing its use as a nanocarrier for drug delivery systems. The stealth property of PEG that composes the outer layer of nanoplatforms, makes the micelle unperceivable to phagocytic cells, increasing the circulation time in the human body. In addition, folic acid functionalization enables micelle selectively targeting to cancer cells, improving treatment efficiency and reducing side effects. In this work, PEG-b-PCL copolymer was synthesized by ring opening polymerization (ROP) of the ε-caprolactone with Poly(ethylene glycol) as a macroinitiator and tin(II) 2-ethyl hexanoate as a catalyst. Functionalization of such micelles with folic acid occurred through the modification of the PEG terminal group. The surface modification of the copolymer micelles resulted in higher critical micellar concentration (CMC), increasing approximately 100 times. The synthesis of the copolymers resulted in molecular weight around 3000 g mol −1 with low polydispersity. The polymer micelles have a hydrodynamic diameter in the range of 100–200 nm and the functionalized sample doesn't show aggregation in the considered pH range. High incorporation efficiency was obtained with a minimum percentage of 85%. The drug release profile and linearization from the Peppas model confirmed the interaction of methotrexate with the hydrophobic segment of the copolymer and its release mechanism by relaxation and/or degradation of the chains, making PEG-b-PCL micelles suitable candidates for hydrophobic drug delivery systems.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Department of Physical Chemistry Institute of Chemistry São Paulo State University (UNESP)Department of Chemistry Center of Nanotechnology and Tissue Engineering –Photobiology and Photomedicine Research Group Faculty of Philosophy Science and Letters of Ribeirão Preto University of São Paulo (USP)Department of Bioprocess and Biotechnology School of Pharmaceutical Sciences São Paulo State University (UNESP)Department of Physical Chemistry Institute of Chemistry São Paulo State University (UNESP)Department of Bioprocess and Biotechnology School of Pharmaceutical Sciences São Paulo State University (UNESP)Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Brandt, João Victor [UNESP]Piazza, Rodolfo Debone [UNESP]dos Santos, Caio Carvalho [UNESP]Vega-Chacón, Jaime [UNESP]Amantéa, Bruno Estevam [UNESP]Pinto, Gabriel Cardoso [UNESP]Magnani, Marina [UNESP]Piva, Henrique LuísTedesco, Antonio ClaudioPrimo, Fernando Lucas [UNESP]Jafelicci, Miguel [UNESP]Marques, Rodrigo Fernando Costa [UNESP]2019-10-06T16:16:35Z2019-10-06T16:16:35Z2019-05-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article228-234http://dx.doi.org/10.1016/j.colsurfb.2019.02.008Colloids and Surfaces B: Biointerfaces, v. 177, p. 228-234.1873-43670927-7765http://hdl.handle.net/11449/18870410.1016/j.colsurfb.2019.02.0082-s2.0-8506118132221159426216941740000-0003-0195-3885Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengColloids and Surfaces B: Biointerfacesinfo:eu-repo/semantics/openAccess2021-10-22T20:11:30Zoai:repositorio.unesp.br:11449/188704Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T18:59:35.637223Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate delivery
title Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate delivery
spellingShingle Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate delivery
Brandt, João Victor [UNESP]
Copolymer micelles
Methotrexate
PEG-b-PCL
Targeted drug delivery
title_short Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate delivery
title_full Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate delivery
title_fullStr Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate delivery
title_full_unstemmed Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate delivery
title_sort Synthesis and colloidal characterization of folic acid-modified PEG-b-PCL Micelles for methotrexate delivery
author Brandt, João Victor [UNESP]
author_facet Brandt, João Victor [UNESP]
Piazza, Rodolfo Debone [UNESP]
dos Santos, Caio Carvalho [UNESP]
Vega-Chacón, Jaime [UNESP]
Amantéa, Bruno Estevam [UNESP]
Pinto, Gabriel Cardoso [UNESP]
Magnani, Marina [UNESP]
Piva, Henrique Luís
Tedesco, Antonio Claudio
Primo, Fernando Lucas [UNESP]
Jafelicci, Miguel [UNESP]
Marques, Rodrigo Fernando Costa [UNESP]
author_role author
author2 Piazza, Rodolfo Debone [UNESP]
dos Santos, Caio Carvalho [UNESP]
Vega-Chacón, Jaime [UNESP]
Amantéa, Bruno Estevam [UNESP]
Pinto, Gabriel Cardoso [UNESP]
Magnani, Marina [UNESP]
Piva, Henrique Luís
Tedesco, Antonio Claudio
Primo, Fernando Lucas [UNESP]
Jafelicci, Miguel [UNESP]
Marques, Rodrigo Fernando Costa [UNESP]
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Universidade de São Paulo (USP)
dc.contributor.author.fl_str_mv Brandt, João Victor [UNESP]
Piazza, Rodolfo Debone [UNESP]
dos Santos, Caio Carvalho [UNESP]
Vega-Chacón, Jaime [UNESP]
Amantéa, Bruno Estevam [UNESP]
Pinto, Gabriel Cardoso [UNESP]
Magnani, Marina [UNESP]
Piva, Henrique Luís
Tedesco, Antonio Claudio
Primo, Fernando Lucas [UNESP]
Jafelicci, Miguel [UNESP]
Marques, Rodrigo Fernando Costa [UNESP]
dc.subject.por.fl_str_mv Copolymer micelles
Methotrexate
PEG-b-PCL
Targeted drug delivery
topic Copolymer micelles
Methotrexate
PEG-b-PCL
Targeted drug delivery
description Hydrophobic drugs, such as methotrexate, are not easily delivered into the human body. Therefore, the use of amphiphilic nanoplatforms to the transport of these drugs through the bloodstream is a challenge. While the hydrophobic region interacts with the drug, the hydrophilic outer layer enhances its bioavailability and circulation time. Poly (ethylene glycol)-block-poly(ε-caprolactone) PEG-b-PCL micelles are biodegradable and biocompatible, allowing its use as a nanocarrier for drug delivery systems. The stealth property of PEG that composes the outer layer of nanoplatforms, makes the micelle unperceivable to phagocytic cells, increasing the circulation time in the human body. In addition, folic acid functionalization enables micelle selectively targeting to cancer cells, improving treatment efficiency and reducing side effects. In this work, PEG-b-PCL copolymer was synthesized by ring opening polymerization (ROP) of the ε-caprolactone with Poly(ethylene glycol) as a macroinitiator and tin(II) 2-ethyl hexanoate as a catalyst. Functionalization of such micelles with folic acid occurred through the modification of the PEG terminal group. The surface modification of the copolymer micelles resulted in higher critical micellar concentration (CMC), increasing approximately 100 times. The synthesis of the copolymers resulted in molecular weight around 3000 g mol −1 with low polydispersity. The polymer micelles have a hydrodynamic diameter in the range of 100–200 nm and the functionalized sample doesn't show aggregation in the considered pH range. High incorporation efficiency was obtained with a minimum percentage of 85%. The drug release profile and linearization from the Peppas model confirmed the interaction of methotrexate with the hydrophobic segment of the copolymer and its release mechanism by relaxation and/or degradation of the chains, making PEG-b-PCL micelles suitable candidates for hydrophobic drug delivery systems.
publishDate 2019
dc.date.none.fl_str_mv 2019-10-06T16:16:35Z
2019-10-06T16:16:35Z
2019-05-01
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.colsurfb.2019.02.008
Colloids and Surfaces B: Biointerfaces, v. 177, p. 228-234.
1873-4367
0927-7765
http://hdl.handle.net/11449/188704
10.1016/j.colsurfb.2019.02.008
2-s2.0-85061181322
2115942621694174
0000-0003-0195-3885
url http://dx.doi.org/10.1016/j.colsurfb.2019.02.008
http://hdl.handle.net/11449/188704
identifier_str_mv Colloids and Surfaces B: Biointerfaces, v. 177, p. 228-234.
1873-4367
0927-7765
10.1016/j.colsurfb.2019.02.008
2-s2.0-85061181322
2115942621694174
0000-0003-0195-3885
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Colloids and Surfaces B: Biointerfaces
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 228-234
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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