Application of polymeric nanoparticles prepared by an antisolvent diffusion with preferential solvation for iontophoretic transdermal drug delivery

摘要

Indomethacin-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles with an average diameter of 100 nm were prepared by using a combination of an antisolvent diffusion method with preferential solvation (bare nanoparticles). Polyvinyl alcohol (PVA)-coated indomethacin-loaded PLGA nanoparticles with an average diameter of 100 nm were also prepared by emulsification and the solvent evaporation method (PVA-coated nanoparticles). Bare nanoparticles do not have a hydrophilic stabilizer on the surface; therefore, they have high hydrophobiciry and negative charges. Electrophoretic mobility of bare nanoparticles at 5 mM NaCl solution was about 68 times higher than that of PVA-coated nanoparticles. Permeability of bare nanoparticles through rat skin was significantly higher than that of PVA-coated nanoparticles when iontophoresis was applied ex vivo. Indomethacin amount inside the skin after the permeation study by using bare nanoparticles was much higher than that by using PVA-coated nanoparticles. Indomethacin transition to circulation and accumulation in muscle by the transdermal delivery of indomethacin-loaded PLGA nanoparticles were significantly enhanced by using the combination of bare nanoparticles and iontophoresis in vivo. As for transdermal route of nanoparticles, both bare and PVA-coated nanoparticles were revealed to penetrate through the transfollicular pathway, and the migration of nanoparticles to follicles was enhanced by the application of iontophoresis. PLGA nanoparticles prepared by the antisolvent diffusion with preferential solvation are beneficial for iontophoretic transdermal delivery of therapeutic agents.