Surfactant free preparation of PLGA nanoparticles: The combination of antisolvent diffusion with preferential solvation

Abstract

Indomethacin-loaded PLGA nanoparticles with an average diameter of 100nm were prepared by using a combination of an antisolvent diffusion method with preferential solvation (bare nanoparticles). For bare nanoparticles, the number density of negative charges on their surfaces was calculated to be −47.57mM, while the number density of negative charges on the surfaces of indomethacin-loaded PLGA nanoparticles prepared by emulsification and the solvent evaporation method (PVA-coated nanoparticles) was −0.23mM. The bare nanoparticles do not have a hydrophilic stabilizer on the surface; therefore, they have high hydrophobicity and negative charges. On the other hand, PVA-coated nanoparticles have a hydrophilic stabilizer (polyvinyl alcohol; PVA) on the surface. Thus the degree of hydrophobicity is low by the amphiphilic property of PVA, and the negative charge is also low by charge shielding effect of PVA. Electrophoretic mobilities of bare nanoparticles were 59–68 times higher than those of PVA-coated nanoparticles, at the measurement range of ionic strength of PBS buffer (pH 7.4) in this experiment. These results suggest that nanoparticles prepared by the antisolvent diffusion method with preferential solvation have a higher potential to be affected by electrical energy than nanoparticles prepared by emulsification with the solvent evaporation method. Skin permeability test ex vivo confirmed that the bare nanoparticles can be more affected by iontophoresis than the PVA-coated nanoparticles. Thus the nanoparticles prepared by the antisolvent diffusion method with preferential solvation are beneficial for the iontophoretic transdermal delivery of therapeutic agents.