Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitation
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.ijpharm.2017.03.068 http://hdl.handle.net/11449/178792 |
Resumo: | Development of nanosuspensions offers a promising tool for formulations involving poorly water-soluble drugs. In this study, methotrexate (MTX) nanosuspensions were prepared using a bottom-up process based on acid-base neutralization reactions. Computational studies were performed to determine structural and electronic properties for isolated molecules and molecular clusters in order to evaluate the mechanism of MTX nanoparticle formation. Computational results indicated that the clusters in zwitterionic and cationic states presented larger dimensions and higher energies of interaction between MTX molecules, which favored aggregation. In contrast, the clusters in the anionic state exhibited lower energies of interaction, indicating aggregation was less likely to occur. Experimental results indicated that the higher the HCl proportion during drug precipitation, the greater the particle size, resulting in micrometric particles (2874–7308 nm) (cationic and zwitterionic forms). However, MTX nanoparticles ranging in size from 132 to 186 nm were formed using the lowest HCl proportion during drug precipitation (anionic form). In vitro release profiles indicated that the drug release rate from nanosuspension was increased (approximately 2.6 times) over that of the raw material. Overall, computational modeling and experimental analysis were complementary and assisted in the rational design of the nanosuspension based on acid-base reactions. |
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Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitationAcid-base neutralizationBottom-up processComputational modelingMethotrexateNanosuspensionsDevelopment of nanosuspensions offers a promising tool for formulations involving poorly water-soluble drugs. In this study, methotrexate (MTX) nanosuspensions were prepared using a bottom-up process based on acid-base neutralization reactions. Computational studies were performed to determine structural and electronic properties for isolated molecules and molecular clusters in order to evaluate the mechanism of MTX nanoparticle formation. Computational results indicated that the clusters in zwitterionic and cationic states presented larger dimensions and higher energies of interaction between MTX molecules, which favored aggregation. In contrast, the clusters in the anionic state exhibited lower energies of interaction, indicating aggregation was less likely to occur. Experimental results indicated that the higher the HCl proportion during drug precipitation, the greater the particle size, resulting in micrometric particles (2874–7308 nm) (cationic and zwitterionic forms). However, MTX nanoparticles ranging in size from 132 to 186 nm were formed using the lowest HCl proportion during drug precipitation (anionic form). In vitro release profiles indicated that the drug release rate from nanosuspension was increased (approximately 2.6 times) over that of the raw material. Overall, computational modeling and experimental analysis were complementary and assisted in the rational design of the nanosuspension based on acid-base reactions.Department of Drugs and Pharmaceutics Faculty of Pharmaceutical Sciences São Paulo State University-UNESPFaculty of Pharmaceutical Sciences Federal University of Alfenas-UNIFALFederal Institute of Mato Grosso-IFMTInstitute of Physical—University of Brasília-UnBDepartment of Drugs and Pharmaceutics Faculty of Pharmaceutical Sciences São Paulo State University-UNESPUniversidade Estadual Paulista (Unesp)Federal University of Alfenas-UNIFALFederal Institute of Mato Grosso-IFMTInstitute of Physical—University of Brasília-UnBdos Santos, Aline Martins [UNESP]Carvalho, Flávia ChivaTeixeira, Deiver AlessandroAzevedo, David Limade Barros, Wander MiguelGremião, Maria Palmira Daflon [UNESP]2018-12-11T17:32:06Z2018-12-11T17:32:06Z2017-05-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article330-338application/pdfhttp://dx.doi.org/10.1016/j.ijpharm.2017.03.068International Journal of Pharmaceutics, v. 524, n. 1-2, p. 330-338, 2017.1873-34760378-5173http://hdl.handle.net/11449/17879210.1016/j.ijpharm.2017.03.0682-s2.0-850173996332-s2.0-85017399633.pdf9129780536724256Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengInternational Journal of Pharmaceutics1,172info:eu-repo/semantics/openAccess2024-06-24T13:46:11Zoai:repositorio.unesp.br:11449/178792Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-06-24T13:46:11Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitation |
title |
Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitation |
spellingShingle |
Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitation dos Santos, Aline Martins [UNESP] Acid-base neutralization Bottom-up process Computational modeling Methotrexate Nanosuspensions |
title_short |
Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitation |
title_full |
Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitation |
title_fullStr |
Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitation |
title_full_unstemmed |
Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitation |
title_sort |
Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitation |
author |
dos Santos, Aline Martins [UNESP] |
author_facet |
dos Santos, Aline Martins [UNESP] Carvalho, Flávia Chiva Teixeira, Deiver Alessandro Azevedo, David Lima de Barros, Wander Miguel Gremião, Maria Palmira Daflon [UNESP] |
author_role |
author |
author2 |
Carvalho, Flávia Chiva Teixeira, Deiver Alessandro Azevedo, David Lima de Barros, Wander Miguel Gremião, Maria Palmira Daflon [UNESP] |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Federal University of Alfenas-UNIFAL Federal Institute of Mato Grosso-IFMT Institute of Physical—University of Brasília-UnB |
dc.contributor.author.fl_str_mv |
dos Santos, Aline Martins [UNESP] Carvalho, Flávia Chiva Teixeira, Deiver Alessandro Azevedo, David Lima de Barros, Wander Miguel Gremião, Maria Palmira Daflon [UNESP] |
dc.subject.por.fl_str_mv |
Acid-base neutralization Bottom-up process Computational modeling Methotrexate Nanosuspensions |
topic |
Acid-base neutralization Bottom-up process Computational modeling Methotrexate Nanosuspensions |
description |
Development of nanosuspensions offers a promising tool for formulations involving poorly water-soluble drugs. In this study, methotrexate (MTX) nanosuspensions were prepared using a bottom-up process based on acid-base neutralization reactions. Computational studies were performed to determine structural and electronic properties for isolated molecules and molecular clusters in order to evaluate the mechanism of MTX nanoparticle formation. Computational results indicated that the clusters in zwitterionic and cationic states presented larger dimensions and higher energies of interaction between MTX molecules, which favored aggregation. In contrast, the clusters in the anionic state exhibited lower energies of interaction, indicating aggregation was less likely to occur. Experimental results indicated that the higher the HCl proportion during drug precipitation, the greater the particle size, resulting in micrometric particles (2874–7308 nm) (cationic and zwitterionic forms). However, MTX nanoparticles ranging in size from 132 to 186 nm were formed using the lowest HCl proportion during drug precipitation (anionic form). In vitro release profiles indicated that the drug release rate from nanosuspension was increased (approximately 2.6 times) over that of the raw material. Overall, computational modeling and experimental analysis were complementary and assisted in the rational design of the nanosuspension based on acid-base reactions. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-05-30 2018-12-11T17:32:06Z 2018-12-11T17:32:06Z |
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.ijpharm.2017.03.068 International Journal of Pharmaceutics, v. 524, n. 1-2, p. 330-338, 2017. 1873-3476 0378-5173 http://hdl.handle.net/11449/178792 10.1016/j.ijpharm.2017.03.068 2-s2.0-85017399633 2-s2.0-85017399633.pdf 9129780536724256 |
url |
http://dx.doi.org/10.1016/j.ijpharm.2017.03.068 http://hdl.handle.net/11449/178792 |
identifier_str_mv |
International Journal of Pharmaceutics, v. 524, n. 1-2, p. 330-338, 2017. 1873-3476 0378-5173 10.1016/j.ijpharm.2017.03.068 2-s2.0-85017399633 2-s2.0-85017399633.pdf 9129780536724256 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
International Journal of Pharmaceutics 1,172 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
330-338 application/pdf |
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_ |
1803045472252723200 |