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

Li, Fangfei, Gorle, Anil K., Ranson, Marie, Vine, Kara L., Kinobe, Robert, Feterl, Marshall, Warner, Jeffrey M., Keene, F. Richard, Collins, J. Grant, and Day, Anthony I. (2017) Probing the pharmacokinetics of cucurbit[7, 8 and 10]uril: and a dinuclear ruthenium antimicrobial complex encapsulated in cucurbit[10]uril. Organic and Biomolecular Chemistry, 15 (19). pp. 4172-4179.

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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.

Item ID: 48934
Item Type: Article (Research - C1)
ISSN: 1477-0539
Keywords: pharmacokinetics; cucurbit[n]uril; antimicrobial; dinuclear ruthenium complex; drug delivery
Funders: NewSouth Innovations (NSi), National Health and Medical Research Council (NHMRC)
Projects and Grants: NSi Commercialising Emerging Technologies (COMET) grant 2009, NHMRC Development Grant 514644
Date Deposited: 15 May 2017 01:00
FoR Codes: 03 CHEMICAL SCIENCES > 0302 Inorganic Chemistry > 030201 Bioinorganic Chemistry @ 20%
03 CHEMICAL SCIENCES > 0304 Medicinal and Biomolecular Chemistry > 030401 Biologically Active Molecules @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110899 Medical Microbiology not elsewhere classified @ 40%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970103 Expanding Knowledge in the Chemical Sciences @ 40%
97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 30%
97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 30%
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