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Simvastatin Coadministration Modulates the Electrostatically Driven Incorporation of Doxorubicin into Model Lipid and Cell Membranes

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cris.lastimport.scopus2024-02-12T20:13:02Z
dc.abstract.enUnderstanding the interactions between drugs and lipid membranes is a prerequisite for finding the optimal way to deliver drugs into cells. Coadministration of statins and anticancer agents has been reported to have a positive effect on anticancer therapy. In this study, we elucidate the mechanism by which simvastatin (SIM) improves the efficiency of biological membrane penetration by the chemotherapeutic agent doxorubicin (DOX) in neutral and slightly acidic solutions. The incorporation of DOX, SIM, or a combination of them (DOX:SIM) into selected single-component lipid membranes, zwitterionic unsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), neutral cholesterol, and negatively charged 1,2-dimyristoyl-sn-glycero-3-phospho-l-serine (DMPS) was assessed using the Langmuir method. The penetration of neutral lipid monolayers by the codelivery of SIM and DOX was clearly facilitated at pH 5.5, which resembles the pH conditions of the environment of cancer cells. This effect was ascribed to partial neutralization of the DOX positive charge as the result of intermolecular interactions between DOX and SIM. On the other hand, the penetration of the negatively charged DMPS monolayer was most efficient in the case of the positively charged DOX. The efficiency of the drug delivery to the cell membranes was evaluated under in vitro conditions using a panel of cancer-derived cell lines (A172, T98G, and HeLa). MTS and trypan blue exclusion assays were performed, followed by confocal microscopy and spheroid culture tests. Cells were exposed to either free drugs or drugs encapsulated in lipid carriers termed cubosomes. We demonstrated that the viability of cancer cells exposed to DOX was significantly impaired in the presence of SIM, and this phenomenon was greatly magnified when DOX and SIM were coencapsulated in cubosomes. Overall, our results confirmed the utility of the DOX:SIM combination delivery, which enhances the interactions between neutral components of cell membranes and positively charged chemotherapeutic agents.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorBilewicz, Renata
dc.contributor.authorNazaruk, Ewa
dc.contributor.authorJabłonowska, Elżbieta
dc.contributor.authorGaweł, Damian
dc.contributor.authorGodlewska, Marlena
dc.contributor.authorGajda, Ewa
dc.contributor.authorBartkowiak, Aleksandra
dc.date.accessioned2024-01-26T07:38:47Z
dc.date.available2024-01-26T07:38:47Z
dc.date.copyright2022-09-29
dc.date.issued2022
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.number10
dc.description.versionFINAL_PUBLISHED
dc.description.volume8
dc.identifier.doi10.1021/ACSBIOMATERIALS.2C00724
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/119864
dc.identifier.weblinkhttps://pubs.acs.org/doi/pdf/10.1021/acsbiomaterials.2c00724
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofACS Biomaterial Science and Engineering
dc.relation.pages4354-4364
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enSimvastatin
dc.subject.enDoxorubicin
dc.subject.enCubosomes
dc.subject.enLangmuir monolayer
dc.subject.enCancer cells
dc.titleSimvastatin Coadministration Modulates the Electrostatically Driven Incorporation of Doxorubicin into Model Lipid and Cell Membranes
dc.typeJournalArticle
dspace.entity.typePublication