title: A cisplatin slow-release hydrogel drug delivery system based on a formulation of the macrocycle cucurbit[7]uril, gelatin and polyvinyl alcohol.
abstract: The anticancer drug cisplatin was encapsulated within the cucurbit[7]uril macrocycle to form the host-guest complex: cisplatin@CB[7]. This was then incorporated into gelatin and 0-4% w/v polyvinyl alcohol (PVA)-based hydrogels as slow release drug delivery vehicles. The hydrogels demonstrated predicable swelling and disintegration dependent on the PVA concentration. The hydrogel with the highest PVA content was slower to swell and release drug compared with lower concentrations of PVA. The effect of the hydrogel PVA concentration on in vitro cytotoxicity was examined using A2780/CP70 ovarian cancer cells. Over the 24h drug exposure time used, hydrogels containing 4% PVA showed a 20% decrease in viable cells compared to the control, whereas hydrogels containing 0% and 2% PVA induced an 80% and 45% inhibition of cell growth, respectively. There was no measurable difference in the in vitro cytotoxicity of free cisplatin and cisplatin@CB[7] containing hydrogels. Finally, the in vivo effectiveness of a 2%-PVA hydrogel implanted under the skin of nude mice bearing A2780/CP70 xenografts showed that low dose hydrogels containing cisplatin@CB[7] (30 μg equivalent of drug) was just as effective as an intraperitoneal high dose administration of free cisplatin (150 μg) at inhibiting tumour growth.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom.
authors.forename: Rabbab
authors.initials: R
authors.lastname: Oun
authors.affiliation: Institute of Cancer Sciences, University of Glasgow, Cancer Research UK Beatson Laboratories, Garscube Estate, Glasgow G61 1BD, United Kingdom.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Plumb
authors.affiliation: Faculty of Pharmacy, The University of Sydney, NSW 2006, Australia. Electronic address: nial.wheate@sydney.edu.au.
authors.forename: Nial J
authors.initials: NJ
authors.lastname: Wheate
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004343:Drug Implants; D005260:Female; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels; D007093:Imidazoles / Q000737:chemistry*; D007274:Injections, Intraperitoneal; D007700:Kinetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D002945:Cisplatin; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005780:Gelatin; D020100:Hydrogels; D007093:Imidazoles; D011142:Polyvinyl Alcohol; C456276:cucurbit(7)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils; C062364:polyvinyl alcohol hydrogel
keywords: Cisplatin; Cucurbituril; Drug delivery; Hydrogel; Polyvinyl alcohol; Slow release