2002 年 62 巻 4 号 p. 189-202
Safety and efficacy information is necessary for drug delivery systems that use particulate systems prepared with copoly (DL-lactic/glycolic acid) (PLGA). To investigate the size-effect of PLGA particulate systems, the present study first evaluated the in vitro cytotoxicity, and then assessed the prolonged efficiency of lidocaine-loaded PLGA nanospheres. PLGA and fluoresceinamine-bound PLGA (FA-PLGA) nanospheres and microspheres were prepared by the modified emulsion solvent diffusion method. Comparative in vitro cytotoxicity studies of PLGA nanospheres and microspheres were evaluated by the direct contact method using the L929 cell culture model; WST-1(2-(4-lodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazollum-Na) assay and LDH (lactate dehydrogenase) release. The fluorescence microscopy method was used to identify the phagocytosed PLGA particulate systems by cultured L929 cells. These in vitro cytotoxicity tests showed that PLGA microspheres were safer than PLGA nanospheres. The PLGA nanospheres were phagocytosed into the L929 cells. To confirm the pharmacological effect of lidocaine-loaded PLGA particulate systems, localized pain-responses were assessed using the subcutaneously administered anesthetic guinea pig model. Lidocaine-loaded PLGA nanospheres were found to provide remarkably prolonged local anesthetic effects compared with lidocaine solution.
