Skin permeability and transdermal delivery route of 50-nm indomethacin-loaded PLGA nanoparticles

Abstract

Recently, nano-seized systems for transdermal delivery have attracted attention. To efficiently deliver drugs to hair follicles, we focused on poly(DL-lactide-co-glycolide) (PLGA) nanoparticles prepared using a combination of an antisolvent diffusion method with preferential solvation. The PLGA nanoparticles prepared using this method are suitable for iontophoresis because of their high surface charge number density. It has been reported that PLGA nanoparticles were delivered to hair follicles by applying iontophoresis, however research on PLGA nanoparticles with a size of less than 100nm was lacking. In this study, we prepared 50-nm and 100-nm PLGA nanoparticles. Indomethacin was used as a hydrophobic drug model and the nanoparticles were evaluated their skin permeability using the abdominal skin of a rat. Two hours after administration, the skin permeation indomethacin amounts of 50-nm and 100-nm PLGA nanoparticles with iontophoresis were significantly higher than those of passively diffused nanoparticles and indomethacin solution. Moreover, when iontophoresis was applied, the indomethacin concentration in the rat skin of 50-nm PLGA nanoparticles was 1.7 times higher than that of 100-nm PLGA nanoparticles. We also prepared coumarin-6-loaded 50-nm and 100-nm PLGA nanoparticles having surface characteristics equivalent to those of indomethacin-loaded PLGA nanoparticles to investigate transdermal delivery route of indomethacin-loaded PLGA nanoparticles. The 50-nm nanoparticles reached a deeper portion of the hair follicle when applying iontophoresis. Therefore, it was shown that this nanoparticle was useful for targeting to hair follicles.