Praziquantel-Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug

Praziquantel is an antiparasitic drug indicated for the treatment of the schistosomiasis disease. This drug has very low aqueous solubility, requiring high oral doses for its administration which gives rise to side effects, therapeutic noncompliance and the appearance of resistant forms of the paras...

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Autores: Borrego Sánchez, Ana, Sánchez Espejo, Rita, García-Villén, Fátima, Viseras, César, Sainz-Díaz, C. Ignacio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/235124
Acceso en línea:http://hdl.handle.net/10261/235124
Access Level:acceso abierto
Palabra clave:Praziquantel
Drug
Montmorillonite
Sepiolite
Organic solvents
Cytotoxicity
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spelling Praziquantel-Clays as Accelerated Release Systems to Enhance the Low Solubility of the DrugBorrego Sánchez, AnaSánchez Espejo, RitaGarcía-Villén, FátimaViseras, CésarSainz-Díaz, C. IgnacioPraziquantelDrugMontmorilloniteSepioliteOrganic solventsCytotoxicityPraziquantel is an antiparasitic drug indicated for the treatment of the schistosomiasis disease. This drug has very low aqueous solubility, requiring high oral doses for its administration which gives rise to side effects, therapeutic noncompliance and the appearance of resistant forms of the parasite. Clay minerals, like sepiolite and montmorillonite, are innocuous, non-toxic, biocompatible and low-cost excipients. Additionally, clays have high adsorbent properties that allow them to encapsulate drugs in nanometric spaces present in the channels in the case of the sepiolite or between the layers in the case of the montmorillonite. The interactions between the drug and clay minerals are studied experimentally with the strategy for preparing interactions products in organic solvents (ethanol, acetonitrile and dichloromethane) so that the interaction will be more effective and will be enhanced the aqueous solubility of praziquantel. The results showed that in the interaction products, the drug interacted with both clay minerals, which produced the loss of the crystallinity of the drug demonstrated by different techniques. This led to a significant increase in the dissolution rate of the praziquantel in all the interaction products in the simulated gastrointestinal tract media, except for the praziquantel¿montmorillonite product prepared in dichloromethane that presented a controlled release in acid medium. Moreover, in vitro cytotoxicity and cell cycle studies were performed in the interaction products prepared with ethanol. The interaction product with sepiolite was biocompatible with the HTC116 line cells, and it did not produce alterations in the cell cycle. However, interaction products with montmorillonite did not produce cell death, but they showed affectation and damage of cells in the cell cycle study at the highest concentration tested (20¿100 µM). Therefore, the different organic solvents used are adequate for the improvement of the biopharmaceutical profile of praziquantel. Drug¿clay interaction products, specifically with sepiolite, showed very promising results in which new accelerated oral release systems of the praziquantel were obtainedThis research was funded by Ministerio de Ciencia e Innovación government, grants numbers PCIN-2017-098, FIS2016-77692-C2-2-P and CGL2016-80833-R and by Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía government, grants numbers RNM1897 and P18-RT-3786.Multidisciplinary Digital Publishing InstituteMinisterio de Ciencia e Innovación (España)Junta de AndalucíaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/235124reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PCIN-2017-098info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/FIS2016-77692-C2-2-Pinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CGL2016-80833-Rhttp://dx.doi.org/10.3390/pharmaceutics12100914Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2351242026-05-22T06:33:51Z
dc.title.none.fl_str_mv Praziquantel-Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug
title Praziquantel-Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug
spellingShingle Praziquantel-Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug
Borrego Sánchez, Ana
Praziquantel
Drug
Montmorillonite
Sepiolite
Organic solvents
Cytotoxicity
title_short Praziquantel-Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug
title_full Praziquantel-Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug
title_fullStr Praziquantel-Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug
title_full_unstemmed Praziquantel-Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug
title_sort Praziquantel-Clays as Accelerated Release Systems to Enhance the Low Solubility of the Drug
dc.creator.none.fl_str_mv Borrego Sánchez, Ana
Sánchez Espejo, Rita
García-Villén, Fátima
Viseras, César
Sainz-Díaz, C. Ignacio
author Borrego Sánchez, Ana
author_facet Borrego Sánchez, Ana
Sánchez Espejo, Rita
García-Villén, Fátima
Viseras, César
Sainz-Díaz, C. Ignacio
author_role author
author2 Sánchez Espejo, Rita
García-Villén, Fátima
Viseras, César
Sainz-Díaz, C. Ignacio
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Junta de Andalucía
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Praziquantel
Drug
Montmorillonite
Sepiolite
Organic solvents
Cytotoxicity
topic Praziquantel
Drug
Montmorillonite
Sepiolite
Organic solvents
Cytotoxicity
description Praziquantel is an antiparasitic drug indicated for the treatment of the schistosomiasis disease. This drug has very low aqueous solubility, requiring high oral doses for its administration which gives rise to side effects, therapeutic noncompliance and the appearance of resistant forms of the parasite. Clay minerals, like sepiolite and montmorillonite, are innocuous, non-toxic, biocompatible and low-cost excipients. Additionally, clays have high adsorbent properties that allow them to encapsulate drugs in nanometric spaces present in the channels in the case of the sepiolite or between the layers in the case of the montmorillonite. The interactions between the drug and clay minerals are studied experimentally with the strategy for preparing interactions products in organic solvents (ethanol, acetonitrile and dichloromethane) so that the interaction will be more effective and will be enhanced the aqueous solubility of praziquantel. The results showed that in the interaction products, the drug interacted with both clay minerals, which produced the loss of the crystallinity of the drug demonstrated by different techniques. This led to a significant increase in the dissolution rate of the praziquantel in all the interaction products in the simulated gastrointestinal tract media, except for the praziquantel¿montmorillonite product prepared in dichloromethane that presented a controlled release in acid medium. Moreover, in vitro cytotoxicity and cell cycle studies were performed in the interaction products prepared with ethanol. The interaction product with sepiolite was biocompatible with the HTC116 line cells, and it did not produce alterations in the cell cycle. However, interaction products with montmorillonite did not produce cell death, but they showed affectation and damage of cells in the cell cycle study at the highest concentration tested (20¿100 µM). Therefore, the different organic solvents used are adequate for the improvement of the biopharmaceutical profile of praziquantel. Drug¿clay interaction products, specifically with sepiolite, showed very promising results in which new accelerated oral release systems of the praziquantel were obtained
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/235124
url http://hdl.handle.net/10261/235124
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PCIN-2017-098
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/FIS2016-77692-C2-2-P
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CGL2016-80833-R
http://dx.doi.org/10.3390/pharmaceutics12100914
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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