title: Silica-installed redox nanoparticles for novel oral nanotherapeutics - improvement in intestinal delivery with anti-inflammatory effects.
abstract: Silica nanoparticles were synthesized via a sol-gel method in which tetraethyl orthosilicate was hydrolyzed by the alkaline core of the nitroxide radical-containing nanoparticle (RNP). The silica nanoparticles were successively captured in the RNP core to obtain silica/RNP nanocomposite (siRNP). Alternatively, siRNP was prepared using commercially available silica nanoparticles. The amount of elemental Si present in the siRNPs was controlled from 3 wt% to 12 wt%. Notably, the obtained siRNPs were stable in acidic media, whereas the starting RNP disintegrated immediately. Crosslinking of the RNP by the entrapped silica might improve stability of the siRNPs under such acidic conditions. Rebamipide was found to be stably encapsulated in the cores of the prepared siRNPs even under acidic conditions, probably due to the both basic environment of the cores and absorption tendencies of the entrapped silica. Under neutral to alkaline conditions, release of the rebamipide is accelerated, which is probably due to the repulsion between the anionic silica surface and the anionic rebamipide. Rebamipide-loaded siRNPs (rebamipide@siRNP) were orally administered to mice, and the plasma level of rebamipide was checked at predetermined time intervals, showing a significantly higher uptake of rebamipide in the plasma when compared to orally-administered free rebamipide. Because siRNP possesses nitroxide radicals in the core, it is confirmed that dextran sodium sulfate-induced colon inflammation was effectively suppressed by the oral administration of rebamipide@siRNP in mice.
authors: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba , Tennodai, Tsukuba, Ibaraki , Japan .
authors: Md Amran
authors: MA
authors: Hossain
authors: Mayo
authors: M
authors: Yamashita
authors: Long Binh
authors: LB
authors: Vong
authors: Yutaka
authors: Y
authors: Ikeda
authors: Yukio
authors: Y
authors: Nagasaki
mesh_terms: D000284:Administration, Oral; D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D003092:Colitis / Q000188:drug therapy / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004339:Drug Compounding; D065546:Drug Liberation; D008297:Male; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry*; D009589:Nitrogen Oxides / Q000737:chemistry*; D010084:Oxidation-Reduction; D015363:Quinolones / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D009589:Nitrogen Oxides; D015363:Quinolones; D012822:Silicon Dioxide; C039900:nitroxyl; C052785:rebamipide; D000409:Alanine
keywords: Nanoreactor; nitroxide radical; oral drug delivery; rebamipide; silica nanocomposite