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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
Statement of
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:
Appears in Collections:Chemistry publications

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