title: Layered inorganic nanocomposites: a promising carrier for 5-fluorouracil (5-FU).
abstract: We report here the intercalation of 5-fluorouracil (5-FU), an anticancer drug in interlayer gallery of Na(+) clay (Montmorillonite, MMT), with the assistance of biopolymer (chitosan, CS). The X-ray diffraction patterns, thermal and spectroscopic analyses indicated the drug intercalation into the clay interlayer space in support of CS and stabilized in the longitudinal monolayer by electrostatic interaction. In vitro drug release showed controlled release pattern. The genotoxic effect of drug was in vitro evaluated in human lymphocyte cell culture by comet assay, and results indicated significant reduction in DNA damage when drug was intercalated with clay and formulated in composites. The results of in vitro cell viability assay in cancer cells pointed at decreased toxicity of drug when encapsulated in Na(+)-clay plates than the pristine drug. In vivo pharmacokinetics, biodistribution, hepatotoxicity markers, e.g., SGPT and SGOT, and liver/testicular histology in rats showed plasma/tissue drug levels were within therapeutic window as compared to pristine drug. Therefore, drug-clay hybrid and composites can be of considerable value in chemotherapy of cancer with reduced side effects.
authors.affiliation: Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research Institute, Council of Scientific and Industrial Research (CSIR), Bhavnagar, Gujarat, India.
authors.forename: Bhavesh D
authors.initials: BD
authors.lastname: Kevadiya
authors.forename: Tapan A
authors.initials: TA
authors.lastname: Patel
authors.forename: Devendrasinh D
authors.initials: DD
authors.lastname: Jhala
authors.forename: Rahul P
authors.initials: RP
authors.lastname: Thumbar
authors.forename: Harshad
authors.initials: H
authors.lastname: Brahmbhatt
authors.forename: Maharshi P
authors.initials: MP
authors.lastname: Pandya
authors.forename: Shalini
authors.initials: S
authors.lastname: Rajkumar
authors.forename: Prasant K
authors.initials: PK
authors.lastname: Jena
authors.forename: Ghanshyam V
authors.initials: GV
authors.lastname: Joshi
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Gadhia
authors.forename: C B
authors.initials: CB
authors.lastname: Tripathi
authors.forename: Hari C
authors.initials: HC
authors.lastname: Bajaj
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D001546:Bentonite / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053761:Nanocomposites; D051381:Rats; D017208:Rats, Wistar; D055672:Static Electricity; D014018:Tissue Distribution; D014961:X-Ray Diffraction
chemical_list: D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D001546:Bentonite; D048271:Chitosan; D005472:Fluorouracil