Probing the pharmacokinetics of cucurbit[7, 8 and 10]uril: and a dinuclear ruthenium antimicrobial complex encapsulated in cucurbit[10]uril

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dc.contributor.authorLi, F.
dc.contributor.authorGorle, A.
dc.contributor.authorRanson, M.
dc.contributor.authorVine, K.
dc.contributor.authorKinobe, R.
dc.contributor.authorFeterl, M.
dc.contributor.authorWarner, J.
dc.contributor.authorKeene, F.
dc.contributor.authorCollins, J.
dc.contributor.authorDay, A.
dc.date.issued2017
dc.description.abstractThe relatively non-toxic family of cucurbit[n]uril, Q[n], have shown considerable potential in vitro as drug delivery agents, with only a few examples of pharmacokinetic (PK) studies for drug⊂Q[n]. Drug-free Q[n] PK studies are the next step in determining the pharmacological applicability in their drug delivery potential. The results for the first PK and bio-distribution of drug-free ¹⁴C-Q[7] are described for administration via intravenous (i.v.) and intraperitoneal (i.p.) dosing. A study of oral administration of drug-free ¹⁴C-Q[8] has also been undertaken to determine the time course for the gastrointestinal tract (GIT), absorption and subsequent bio-distribution. Q[10], a potential drug carrier for larger drugs, was evaluated for its effect on the PK profile of a dinuclear ruthenium complex (Rubb₁₂), a potential antimicrobial agent. The Rubb₁₂⊂Q[10] complex and free Rubb₁₂ were administered by i.v. to determine differences in Rubb₁₂ plasma concentrations and organ accumulation. Interestingly, the PK profiles and bio-distribution observed for Q[7] showed similarities to those of Rubb₁₂⊂Q[10]. Drug-free Q[7] has a relatively fast plasma clearance and a generally low organ accumulation except for the kidneys. Drug-free Q[8] showed a low absorption from the GIT into the blood stream but the small percentage absorbed reflected the organ accumulation of Q[7]. These results provide a better understanding of the probable PK profile and bio-distribution for a drug⊂Q[n] through the influence of the drug delivery vehicle and the positive clearance of drug-free Q[n] via the kidneys supports its potential value in future drug delivery applications.
dc.description.statementofresponsibilityFangfei Li, Anil K. Gorle, Marie Ranson, Kara L. Vine, Robert Kinobe, Marshall Feterl, Jeffrey M. Warner, F. Richard Keene, J. Grant Collins and Anthony I. Day
dc.identifier.citationOrganic and Biomolecular Chemistry, 2017; 15(19):4172-4179
dc.identifier.doi10.1039/c7ob00724h
dc.identifier.issn1477-0520
dc.identifier.issn1477-0539
dc.identifier.orcidKeene, F. [0000-0001-7759-0465]
dc.identifier.urihttp://hdl.handle.net/2440/106145
dc.language.isoen
dc.publisherRoyal Society of Chemistry
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/514644
dc.rightsThis journal is © The Royal Society of Chemistry 2017
dc.source.urihttps://doi.org/10.1039/c7ob00724h
dc.subjectAnimals
dc.subjectMice
dc.subjectRuthenium
dc.subjectOrganometallic Compounds
dc.subjectImidazoles
dc.subjectCapsules
dc.subjectAnti-Infective Agents
dc.subjectTissue Distribution
dc.subjectBridged-Ring Compounds
dc.titleProbing the pharmacokinetics of cucurbit[7, 8 and 10]uril: and a dinuclear ruthenium antimicrobial complex encapsulated in cucurbit[10]uril
dc.typeJournal article
pubs.publication-statusPublished

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