title: Effects of covalently bound silica-nitroimidazole drug particles on Entamoeba histolytica.
abstract: Most commonly used antiamoebic drugs are effective in invasive amebiasis, but their response against trophozoites of Entamoeba histolytica, present in the lumen of the human colon, is inadequate. We report the development of an antiamoebic drug carrier that may be effective against luminal infections. Our preparation consists of small silica particles (5-10 microns in diameter) covalently linked to a potent antiamoebic drug, 2-(4-aminophenoxymethyl)-5-nitro-1-methyl imidazole. Silica-drug particles were injected into mice, hamsters, and guinea pigs. We found that trophozoites phagocytosed the particles in vivo and in vitro, followed by rapid cell death due to the released drug. Analysis of mouse serum revealed that no drug was absorbed from the intestine after placement of the drug-containing particles in the intestine. The antiamoebic activity of particles recovered from the intestine was almost fully retained. This novel antiamoebic concept may be useful for luminal therapy for asymptomatic amebiasis and may minimize side effects and frequency of administration.
authors.affiliation: MacArthur Center for Molecular Biology of Parasitic Diseases, Rehovot, Israel.
authors.forename: D
authors.initials: D
authors.lastname: Mirelman
authors.forename: F
authors.initials: F
authors.lastname: De Meester
authors.forename: T
authors.initials: T
authors.lastname: Stolarsky
authors.forename: G D
authors.initials: GD
authors.lastname: Burchard
authors.forename: K
authors.initials: K
authors.lastname: Ernst-Cabrera
authors.forename: M
authors.initials: M
authors.lastname: Wilchek
mesh_terms: D000563:Amebicides / Q000494:pharmacology*; D000818:Animals; D003106:Colon / Q000469:parasitology; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D004748:Entamoeba histolytica / Q000187:drug effects* / Q000254:growth & development; D009593:Nitroimidazoles / Q000494:pharmacology*; D012822:Silicon Dioxide / Q000494:pharmacology*; D013045:Species Specificity
chemical_list: D000563:Amebicides; D009593:Nitroimidazoles; D012822:Silicon Dioxide