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Supersaturable self-microemulsifying delivery systems: an approach to enhance oral bioavailability of benzimidazole anticancer drugs

2021-04Journal article Restricted access
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dc.contributor.authorRosso, Annalisa
dc.contributor.authorAlmouazen, Eyad
dc.contributor.authorPontes, Jorge Filipe
dc.contributor.authorAndretto, Valentina
dc.contributor.authorLeroux, Marine
dc.contributor.authorRomasko, Etienne
dc.contributor.authorAzzouz-Maache, Samira
dc.contributor.authorBordes, Claire
dc.contributor.authorCoste, Isabelle
dc.contributor.authorRenno, Touffic
dc.contributor.authorGiraud, Stephane
dc.contributor.authorBriancon, Stephanie
dc.contributor.authorLollo, Giovanna
dc.date.accessioned2021-09-08T10:58:01Z
dc.date.available2021-09-08T10:58:01Z
dc.date.issued2021-04
dc.description.abstractThis study explored the design of supersaturable self-microemulsifying drug delivery systems (S-SMEDDS) to address poor solubility and oral bioavailability of a novel benzimidazole derivative anticancer drug (BI). Firstly, self-microemulsifying drug delivery systems SMEDDS made of Miglyol (R) 812, Kolliphor (R) RH40, Transcutol (R) HP, and ethanol were prepared and loaded with the BI drug. Upon dispersion, the systems formed neutrally charged droplets of around 20 nm. However, drug precipitation was observed following incubation with simulated gastric fluid (pH 1.2). Aiming at reducing this precipitation and enhancing drug payload, supersaturable systems were then prepared by adding 1% hydroxypropyl cellulose as precipitation inhibitor. Supersaturable systems maintained a higher amount of drug in a supersaturated state in gastric medium compared with conventional formulations and were stable in simulated intestinal medium ( pH 6.8). In vitro cell studies using Caco-2 cell line showed that these formulations reduced in a transient manner the transepithelial electrical resistance of the monolayers without toxicity. Accordingly, confocal images revealed that the systems accumulated at tight junctions after a 2 h exposure. In vivo pharmacokinetic studies carried out following oral administration of BI-loaded S-SMEDDS, SMEDDS, and free drug to healthy mice showed that supersaturable systems promoted drug absorption compared with the other formulations. Overall, these data highlight the potential of using the supersaturable approach as an alternative to conventional SMEDDS for improving oral systemic absorption of lipophilic drugs.
dc.description.sponsorshipNational Research Agency (ANR), HyDNano project French National Research Agency (ANR) [ANR-18-CE18-0025-01]; ANRF rench National Research Agency (ANR) [42306YB]; Fundação para a Ciências e Tecnologia (FCT)Portuguese Foundation for Science and Technology European Commission [42306YB]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1007/s13346-021-00904-x
dc.identifier.issn2190-393X
dc.identifier.urihttp://hdl.handle.net/10400.1/17007
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSpringer
dc.relationCentre of Marine Sciences
dc.subjectSelf-microemulsifying drug delivery system
dc.subjectSupersaturable systems
dc.subjectOral delivery
dc.subjectAnticancer drugs
dc.subject.otherInstruments & Instrumentation; Research & Experimental Medicine; Pharmacology & Pharmacy
dc.titleSupersaturable self-microemulsifying delivery systems: an approach to enhance oral bioavailability of benzimidazole anticancer drugs
dc.typejournal article
dc.typeconference object
dspace.entity.typePublication
oaire.awardTitleCentre of Marine Sciences
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FMulti%2F04326%2F2019/PT
oaire.citation.conferencePlaceUniv Santiago Compostela, Santiago, SPAIN
oaire.citation.endPage691
oaire.citation.issue2
oaire.citation.startPage675
oaire.citation.titleDrug Delivery and Translational Research
oaire.citation.title13th Spanish Portuguese Conference on Controlled Drug Delivery
oaire.citation.volume11
oaire.fundingStream6817 - DCRRNI ID
person.familyNamePontes
person.givenNameJorge Filipe
person.identifier.ciencia-idCB16-5CBD-8B89
person.identifier.orcid0000-0002-6447-0242
person.identifier.scopus-author-id57195033461
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsrestrictedAccess
rcaap.typearticle
rcaap.typeconferenceObject
relation.isAuthorOfPublication3388102a-dcde-4918-81d6-b7b27f34f3ba
relation.isAuthorOfPublication.latestForDiscovery3388102a-dcde-4918-81d6-b7b27f34f3ba
relation.isProjectOfPublicationf38dbd9d-3734-4f3c-8d74-dff8dcaa8674
relation.isProjectOfPublication.latestForDiscoveryf38dbd9d-3734-4f3c-8d74-dff8dcaa8674

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