title: Amphiphilic poly-N-vinylpyrrolidone nanoparticles as carriers for non-steroidal, anti-inflammatory drugs: In vitro cytotoxicity and in vivo acute toxicity study.
abstract: Polymeric nanoparticles were prepared from self-assembled amphiphilic N-vinylpyrrolidone polymers in aqueous media and evaluated as novel carriers of indomethacin, a non-steroidal, anti-inflammatory drug. It was determined that these nanoparticles could be created in spherical morphologies with sizes less than 100nm, narrow size distributions and high indomethacin contents(up to 35%) combined with high drug loading efficiencies(up to 95%). In cytotoxicity tests using the human embryonic stem cell derived fibroblasts (EBF-H9) and hepatocellular carcinoma cells (HepG2), the indomethacin-loaded polymeric nanoparticles showed higher cell viability compared to that of free indomethacin at the same concentration. The median LD50values, determined by the Litchfield-Wilcoxon method, were 55-70mg/kg body weight depending on the polymer molecular design in both mice and rats. Based on the acquired results, these novel amphiphilic poly-N-vinylpyrrolidone nanoparticles can be considered as potential carriers for new, highly efficient, injectable drug delivery systems for hydrophobic drugs such as indomethacin.
authors.affiliation: D. I. Mendeleyev University of Chemical Technology of Russia, Moscow, Russian Federation.
authors.forename: Andrey N
authors.initials: AN
authors.lastname: Kuskov
authors.affiliation: D. I. Mendeleyev University of Chemical Technology of Russia, Moscow, Russian Federation.
authors.forename: Pavel P
authors.initials: PP
authors.lastname: Kulikov
authors.affiliation: D. I. Mendeleyev University of Chemical Technology of Russia, Moscow, Russian Federation.
authors.forename: Anastasia V
authors.initials: AV
authors.lastname: Goryachaya
authors.affiliation: Laboratory of Toxicology, University of Crete, Voutes, Heraklion, Crete, Greece.
authors.forename: Manolis N
authors.initials: MN
authors.lastname: Tzatzarakis
authors.affiliation: Department of Toxicology, University of Medicine and Pharmacy, Faculty of Pharmacy, Craiova, Romania.
authors.forename: Anca O
authors.initials: AO
authors.lastname: Docea
authors.affiliation: Department of Materials Science and Technology, University of Crete, University Campus Voutes, Heraklion, Crete, Greece.
authors.forename: Kelly
authors.initials: K
authors.lastname: Velonia
authors.affiliation: D. I. Mendeleyev University of Chemical Technology of Russia, Moscow, Russian Federation.
authors.forename: Mikhail I
authors.initials: MI
authors.lastname: Shtilman
authors.affiliation: Laboratory of Toxicology, University of Crete, Voutes, Heraklion, Crete, Greece. Electronic address: tsatsaka@uoc.gr.
authors.forename: Aristidis M
authors.initials: AM
authors.lastname: Tsatsakis
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D011205:Povidone / Q000737:chemistry* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D011205:Povidone; D007213:Indomethacin
keywords: Amphiphilic; Drug delivery system; Indomethacin; Nanoparticle; Poly-N-vinylpyrrolidone; Toxicity