Development of PEG-PCL-based polymersomes through design of experiments for co-encapsulation of vemurafenib and doxorubicin as chemotherapeutic drugs
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.molliq.2021.118166 http://hdl.handle.net/11449/230021 |
Resumo: | Nanostructures for co-encapsulation of chemotherapeutic drugs have been widely studied for the last years due to its important advantages, e.g. improved bioavailability and cellular uptake, increased solubility of drugs, and lower chances of multidrug resistance (MDR). In this context, this work describes essential parameters of production and characterization of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) for the co-encapsulation of two chemotherapeutic drugs, doxorubicin (DOX) and vemurafenib (VEM). Three PEG-PCL copolymers were studied, namely PEG45PCL44, PEG114PCL98, and PEG114PCL114. We evaluated the effect of conditions such as stirring speed, stirring time, hydration volume, and ultrasound time in particle size (DH) and polydispersity index (PDI) by two statistical designs (23) to achieve improved (smaller) DH and PDI of PEG-PCL-based Ps. According to our results, the best condition to generate PEG-PCL-based Ps was to employ 1050 rpm of stirring speed by 42 h, a hydration volume of 15 mL (0.05% m/v), and ultrasound by 35 min, resulting in a DH and PDI range of 210 to 245 nm and 0.117 to 0.148, respectively. Moreover, co-encapsulation of DOX and VEM resulted in drug loading ranges of 12 to 18% and 16 to 26% and encapsulation efficiency of 35 to 39% and 43 to 55%, for DOX and VEM, respectively, together with an increase in the DH (i.e., 254 to 282 nm). The Ps nanoformulations were stable at 4, 25, and 37 °C and the release of drugs was faster with the smaller PEG-PCL blocks (i.e., PEG45PCL44 > PEG114PCL98 > PEG114PCL114). The PEG-PCL-based Ps also demonstrated higher drugs release in an acidic environment (i.e., pH 5.0 at 37 °C, found in tumor cells) compared to physiological conditions (pH 7.4 at 37 °C). In conclusion, the DOX/VEM-PEG-PCL-based Ps may be a promising approach to cancer therapy with potential synergic effect, lower dosage, and lower risk of causing MDR. |
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Development of PEG-PCL-based polymersomes through design of experiments for co-encapsulation of vemurafenib and doxorubicin as chemotherapeutic drugsDesign of experiments (DoE)Doxorubicin (DOX)Drug delivery systems (DDS)PEG-PCL copolymersPolymersomes (Ps)Vemurafenib (VEM)Nanostructures for co-encapsulation of chemotherapeutic drugs have been widely studied for the last years due to its important advantages, e.g. improved bioavailability and cellular uptake, increased solubility of drugs, and lower chances of multidrug resistance (MDR). In this context, this work describes essential parameters of production and characterization of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) for the co-encapsulation of two chemotherapeutic drugs, doxorubicin (DOX) and vemurafenib (VEM). Three PEG-PCL copolymers were studied, namely PEG45PCL44, PEG114PCL98, and PEG114PCL114. We evaluated the effect of conditions such as stirring speed, stirring time, hydration volume, and ultrasound time in particle size (DH) and polydispersity index (PDI) by two statistical designs (23) to achieve improved (smaller) DH and PDI of PEG-PCL-based Ps. According to our results, the best condition to generate PEG-PCL-based Ps was to employ 1050 rpm of stirring speed by 42 h, a hydration volume of 15 mL (0.05% m/v), and ultrasound by 35 min, resulting in a DH and PDI range of 210 to 245 nm and 0.117 to 0.148, respectively. Moreover, co-encapsulation of DOX and VEM resulted in drug loading ranges of 12 to 18% and 16 to 26% and encapsulation efficiency of 35 to 39% and 43 to 55%, for DOX and VEM, respectively, together with an increase in the DH (i.e., 254 to 282 nm). The Ps nanoformulations were stable at 4, 25, and 37 °C and the release of drugs was faster with the smaller PEG-PCL blocks (i.e., PEG45PCL44 > PEG114PCL98 > PEG114PCL114). The PEG-PCL-based Ps also demonstrated higher drugs release in an acidic environment (i.e., pH 5.0 at 37 °C, found in tumor cells) compared to physiological conditions (pH 7.4 at 37 °C). In conclusion, the DOX/VEM-PEG-PCL-based Ps may be a promising approach to cancer therapy with potential synergic effect, lower dosage, and lower risk of causing MDR.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Faculty of Pharmaceutical Sciences University of CampinasUniversity of SorocabaDepartment of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP)Department of Pharmacy School of Pharmaceutical Sciences University of São PauloDepartment of Biochemical and Pharmaceutical Technology School of Pharmaceutical Sciences University of São PauloDepartment of Drugs and Medicines School of Pharmaceutical Sciences São Paulo State University (UNESP)CNPq: #123483/2020-4Universidade Estadual de Campinas (UNICAMP)University of SorocabaUniversidade Estadual Paulista (UNESP)Universidade de São Paulo (USP)D'Angelo, Natália A.Câmara, Mayra C.C.Noronha, Mariana A.Grotto, DeniseChorilli, Marlus [UNESP]Lourenço, Felipe R.Rangel-Yagui, Carlota de O.Lopes, André M.2022-04-29T08:37:14Z2022-04-29T08:37:14Z2022-03-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.molliq.2021.118166Journal of Molecular Liquids, v. 349.0167-7322http://hdl.handle.net/11449/23002110.1016/j.molliq.2021.1181662-s2.0-85120832856Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Molecular Liquidsinfo:eu-repo/semantics/openAccess2022-04-29T08:37:14Zoai:repositorio.unesp.br:11449/230021Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462022-04-29T08:37:14Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Development of PEG-PCL-based polymersomes through design of experiments for co-encapsulation of vemurafenib and doxorubicin as chemotherapeutic drugs |
title |
Development of PEG-PCL-based polymersomes through design of experiments for co-encapsulation of vemurafenib and doxorubicin as chemotherapeutic drugs |
spellingShingle |
Development of PEG-PCL-based polymersomes through design of experiments for co-encapsulation of vemurafenib and doxorubicin as chemotherapeutic drugs D'Angelo, Natália A. Design of experiments (DoE) Doxorubicin (DOX) Drug delivery systems (DDS) PEG-PCL copolymers Polymersomes (Ps) Vemurafenib (VEM) |
title_short |
Development of PEG-PCL-based polymersomes through design of experiments for co-encapsulation of vemurafenib and doxorubicin as chemotherapeutic drugs |
title_full |
Development of PEG-PCL-based polymersomes through design of experiments for co-encapsulation of vemurafenib and doxorubicin as chemotherapeutic drugs |
title_fullStr |
Development of PEG-PCL-based polymersomes through design of experiments for co-encapsulation of vemurafenib and doxorubicin as chemotherapeutic drugs |
title_full_unstemmed |
Development of PEG-PCL-based polymersomes through design of experiments for co-encapsulation of vemurafenib and doxorubicin as chemotherapeutic drugs |
title_sort |
Development of PEG-PCL-based polymersomes through design of experiments for co-encapsulation of vemurafenib and doxorubicin as chemotherapeutic drugs |
author |
D'Angelo, Natália A. |
author_facet |
D'Angelo, Natália A. Câmara, Mayra C.C. Noronha, Mariana A. Grotto, Denise Chorilli, Marlus [UNESP] Lourenço, Felipe R. Rangel-Yagui, Carlota de O. Lopes, André M. |
author_role |
author |
author2 |
Câmara, Mayra C.C. Noronha, Mariana A. Grotto, Denise Chorilli, Marlus [UNESP] Lourenço, Felipe R. Rangel-Yagui, Carlota de O. Lopes, André M. |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual de Campinas (UNICAMP) University of Sorocaba Universidade Estadual Paulista (UNESP) Universidade de São Paulo (USP) |
dc.contributor.author.fl_str_mv |
D'Angelo, Natália A. Câmara, Mayra C.C. Noronha, Mariana A. Grotto, Denise Chorilli, Marlus [UNESP] Lourenço, Felipe R. Rangel-Yagui, Carlota de O. Lopes, André M. |
dc.subject.por.fl_str_mv |
Design of experiments (DoE) Doxorubicin (DOX) Drug delivery systems (DDS) PEG-PCL copolymers Polymersomes (Ps) Vemurafenib (VEM) |
topic |
Design of experiments (DoE) Doxorubicin (DOX) Drug delivery systems (DDS) PEG-PCL copolymers Polymersomes (Ps) Vemurafenib (VEM) |
description |
Nanostructures for co-encapsulation of chemotherapeutic drugs have been widely studied for the last years due to its important advantages, e.g. improved bioavailability and cellular uptake, increased solubility of drugs, and lower chances of multidrug resistance (MDR). In this context, this work describes essential parameters of production and characterization of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-PCL)-based polymersomes (Ps) for the co-encapsulation of two chemotherapeutic drugs, doxorubicin (DOX) and vemurafenib (VEM). Three PEG-PCL copolymers were studied, namely PEG45PCL44, PEG114PCL98, and PEG114PCL114. We evaluated the effect of conditions such as stirring speed, stirring time, hydration volume, and ultrasound time in particle size (DH) and polydispersity index (PDI) by two statistical designs (23) to achieve improved (smaller) DH and PDI of PEG-PCL-based Ps. According to our results, the best condition to generate PEG-PCL-based Ps was to employ 1050 rpm of stirring speed by 42 h, a hydration volume of 15 mL (0.05% m/v), and ultrasound by 35 min, resulting in a DH and PDI range of 210 to 245 nm and 0.117 to 0.148, respectively. Moreover, co-encapsulation of DOX and VEM resulted in drug loading ranges of 12 to 18% and 16 to 26% and encapsulation efficiency of 35 to 39% and 43 to 55%, for DOX and VEM, respectively, together with an increase in the DH (i.e., 254 to 282 nm). The Ps nanoformulations were stable at 4, 25, and 37 °C and the release of drugs was faster with the smaller PEG-PCL blocks (i.e., PEG45PCL44 > PEG114PCL98 > PEG114PCL114). The PEG-PCL-based Ps also demonstrated higher drugs release in an acidic environment (i.e., pH 5.0 at 37 °C, found in tumor cells) compared to physiological conditions (pH 7.4 at 37 °C). In conclusion, the DOX/VEM-PEG-PCL-based Ps may be a promising approach to cancer therapy with potential synergic effect, lower dosage, and lower risk of causing MDR. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-04-29T08:37:14Z 2022-04-29T08:37:14Z 2022-03-01 |
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.molliq.2021.118166 Journal of Molecular Liquids, v. 349. 0167-7322 http://hdl.handle.net/11449/230021 10.1016/j.molliq.2021.118166 2-s2.0-85120832856 |
url |
http://dx.doi.org/10.1016/j.molliq.2021.118166 http://hdl.handle.net/11449/230021 |
identifier_str_mv |
Journal of Molecular Liquids, v. 349. 0167-7322 10.1016/j.molliq.2021.118166 2-s2.0-85120832856 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Journal of Molecular Liquids |
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 |
|
_version_ |
1799964377269403648 |