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|Title:||Probing the pharmacokinetics of cucurbit[7, 8 and 10]uril: and a dinuclear ruthenium antimicrobial complex encapsulated in cucurbituril|
|Citation:||Organic and Biomolecular Chemistry, 2017; 15(19):4172-4179|
|Publisher:||Royal Society of Chemistry|
|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 are described for administration via intravenous (i.v.) and intraperitoneal (i.p.) dosing. A study of oral administration of drug-free ¹⁴C-Q has also been undertaken to determine the time course for the gastrointestinal tract (GIT), absorption and subsequent bio-distribution. Q, 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 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 showed similarities to those of Rubb₁₂⊂Q. Drug-free Q has a relatively fast plasma clearance and a generally low organ accumulation except for the kidneys. Drug-free Q showed a low absorption from the GIT into the blood stream but the small percentage absorbed reflected the organ accumulation of Q. 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|
|Appears in Collections:||Chemistry publications|
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