Nanocapsules modify membrane interaction of polymyxin B to enable safe systemic therapy of Gram-negative sepsis

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dc.contributor.authorYuk, Simseok A.en
dc.contributor.authorKim, Hyungjunen
dc.contributor.authorAbutaleb, Nader S.en
dc.contributor.authorDieterly, Alexandra M.en
dc.contributor.authorTaha, Maie S.en
dc.contributor.authorTsifansky, Michael D.en
dc.contributor.authorLyle, L. Tiffanyen
dc.contributor.authorSeleem, Mohamed N.en
dc.contributor.authorYeo, Yoonen
dc.date.accessioned2022-04-06T14:34:57Zen
dc.date.available2022-04-06T14:34:57Zen
dc.date.issued2021-08en
dc.description.abstractSystemic therapy of Gram-negative sepsis remains challenging. Polymyxin B (PMB) is well suited for sepsis therapy due to the endotoxin affinity and antibacterial activity. However, the dose-limiting toxicity has limited its systemic use in sepsis patients. For safe systemic use of PMB, we have developed a nanoparticulate system, called D-TZP, which selectively reduces the toxicity to mammalian cells but retains the therapeutic activities of PMB. D-TZP consists of an iron-complexed tannic acid nanocapsule containing a vitamin D core, coated with PMB and a chitosan derivative that controls the interaction of PMB with endotoxin, bacteria, and host cells. D-TZP attenuated the membrane toxicity associated with PMB but retained the ability of PMB to inactivate endotoxin and kill Gram-negative bacteria. Upon intravenous injection, D-TZP protected animals from pre-established endotoxemia and polymicrobial sepsis, showing no systemic toxicities inherent to PMB. These results support D-TZP as a safe and effective systemic intervention of sepsis.en
dc.description.notesThis work was supported by NIH grant R21 AI119479 (to Y.Y.), the Graduate Assistance in Areas of National Need Fellowship (S.A.Y.), and the Purdue University Institute for Drug Discovery (to Y.Y.).en
dc.description.sponsorshipNIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R21 AI119479]; Graduate Assistance in Areas of National Need Fellowship; Purdue University Institute for Drug Discoveryen
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1126/sciadv.abj1577en
dc.identifier.issn2375-2548en
dc.identifier.issue32en
dc.identifier.othereabj1577en
dc.identifier.pmid34362742en
dc.identifier.urihttp://hdl.handle.net/10919/109571en
dc.identifier.volume7en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleNanocapsules modify membrane interaction of polymyxin B to enable safe systemic therapy of Gram-negative sepsisen
dc.title.serialScience Advancesen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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