Toxic characteristics of methoxy poly(ethylene glycol)/poly(epsilon-caprolactone) nanospheres; in vitro and in vivo studies in the normal mice.

Amphiphilic diblock polymeric nanospheres composed of methoxy poly(ethylene glycol) (MePEG) and poly(epsilon-caprolactone)(PCL) was prepared for application as a novel drug carrier. We could obtain the MePEG/PCL nanospheres that exhibited an average diameter of less than 200 nm with narrow size distribution and a relatively high drug-loading efficiency of about 41.98% and 20.8% for indomethacin and paclitaxel, respectively. To estimate the toxicity of nanospheres, we investigated cytotoxicity using the normal human fibroblast, the median lethal dose (LD(50)) and various organ toxicities using male ICR mice. The indomethacin-loaded nanosphere showed higher cell viability than indomethacin in the cytotoxicity test using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The LD(50) of MePEG/PCL nanospheres determined by Litchfield-Wilcoxon method was 1.47 g/kg. After the mice were intraperitoneally injected with MePEG/PCL nanospheres as a half-dose level of LD(50) for 7 days, no significant histopathologic changes were observed in MePEG/PCL nanospheres-treated mice compared with normal mice in the light and electron microscopic observations of various organs such as heart, lung, liver and kidney. It was suggested that MePEG/PCL nanospheres might be useful candidate as a novel injectable drug carrier for hydrophobic drugs such as indomethacin and paclitaxel. Copyright 2002 Elsevier Science Ltd.