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

Fangfei LI, Anil K. Gorle, Marie Ranson, Kara L. Vine, Robert Kinobe, Marshall Feterl, Jeffrey M. Warner, F. Richard Keene*, J. Grant Collins, Anthony I. Day

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

The 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.

Original languageEnglish
Pages (from-to)4172-4179
Number of pages8
JournalOrganic and Biomolecular Chemistry
Volume15
Issue number19
DOIs
Publication statusPublished - 2017

Scopus Subject Areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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