title: Toxicity of cucurbit[7]uril and cucurbit[8]uril: an exploratory in vitro and in vivo study.
abstract: Cucurbit[n]urils (CB[n]) are potential stabilizing, solubilizing, activating, and delivering agents for drugs. The toxicity of the macrocyclic host molecules cucurbit[7]uril (CB[7]), the most water-soluble homologue, as well as cucurbit[8]uril (CB[8]) has been evaluated. In vitro studies on cell cultures revealed an IC(50) value of 0.53 +/- 0.02 mM for CB[7], corresponding to around 620 mg of CB[7] per kg of cell material. Live-cell imaging studies performed on cells treated with subtoxic amounts of CB[7] showed no detrimental effects on the cellular integrity as assessed by mitochondrial activity. For CB[8], no significant cytotoxicity was observed within its solubility range. The bioadaptability of the compounds was further examined through in vivo studies on mice, where intravenous administration of CB[7] showed a maximum tolerated dosage of 250 mg kg(-1), while oral administration of a CB[7]/CB[8] mixture showed a tolerance of up to 600 mg kg(-1). The combined results indicate a sufficiently low toxicity to encourage further exploration of CB[n] as additives for medicinal and pharmaceutical use.
authors.affiliation: School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, D-28759, Bremen, Germany.
authors.forename: Vanya D
authors.initials: VD
authors.lastname: Uzunova
authors.forename: Carleen
authors.initials: C
authors.lastname: Cullinane
authors.forename: Klaudia
authors.initials: K
authors.lastname: Brix
authors.forename: Werner M
authors.initials: WM
authors.lastname: Nau
authors.forename: Anthony I
authors.initials: AI
authors.lastname: Day
mesh_terms: D000818:Animals; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D013329:Structure-Activity Relationship; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
chemical_list: D001952:Bridged-Ring Compounds; D007093:Imidazoles; C456276:cucurbit(7)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils; C507198:cucurbit(8)uril