Kuskov Andrey N, Kulikov Pavel P, Goryachaya Anastasia V, Tzatzarakis Manolis N, Docea Anca O, Velonia Kelly, Shtilman Mikhail I, Tsatsakis Aristidis M
D. I. Mendeleyev University of Chemical Technology of Russia, Moscow, Russian Federation.
Laboratory of Toxicology, University of Crete, Voutes, Heraklion, Crete, Greece.
Nanomedicine. 2017 Apr;13(3):1021-1030. doi: 10.1016/j.nano.2016.11.006. Epub 2016 Nov 22.
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 LD values, 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.
在水介质中由自组装两亲性N-乙烯基吡咯烷酮聚合物制备了聚合物纳米颗粒,并将其评估为非甾体抗炎药吲哚美辛的新型载体。已确定这些纳米颗粒可以形成尺寸小于100nm的球形形态,具有窄的尺寸分布和高的吲哚美辛含量(高达35%),并结合高的药物负载效率(高达95%)。在使用人胚胎干细胞衍生的成纤维细胞(EBF-H9)和肝癌细胞(HepG2)的细胞毒性试验中,负载吲哚美辛的聚合物纳米颗粒在相同浓度下比游离吲哚美辛表现出更高的细胞活力。根据Litchfield-Wilcoxon方法测定,小鼠和大鼠的半数致死量值中位数为55-70mg/kg体重,具体取决于聚合物分子设计。基于所获得的结果,这些新型两亲性聚N-乙烯基吡咯烷酮纳米颗粒可被视为用于疏水性药物如吲哚美辛的新型、高效、可注射药物递送系统的潜在载体。