Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/106145
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Type: Journal article
Title: Probing the pharmacokinetics of cucurbit[7, 8 and 10]uril: and a dinuclear ruthenium antimicrobial complex encapsulated in cucurbit[10]uril
Author: Li, F.
Gorle, A.
Ranson, M.
Vine, K.
Kinobe, R.
Feterl, M.
Warner, J.
Keene, F.
Collins, J.
Day, A.
Citation: Organic and Biomolecular Chemistry, 2017; 15(19):4172-4179
Publisher: Royal Society of Chemistry
Issue Date: 2017
ISSN: 1477-0520
1477-0539
Statement of
Responsibility: 
Fangfei 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
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.
Keywords: Animals; Mice; Ruthenium; Organometallic Compounds; Imidazoles; Capsules; Anti-Infective Agents; Tissue Distribution; Bridged-Ring Compounds
Rights: This journal is © The Royal Society of Chemistry 2017
RMID: 0030068995
DOI: 10.1039/c7ob00724h
Grant ID: http://purl.org/au-research/grants/nhmrc/514644
Appears in Collections:Chemistry publications

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