Self-assembled macromolecular nanocoatings to stabilize and control drug release from nanoparticles

Abstract

A layer-by-layer (LbL) nanocoat (<25nm thick) of two polyelectrolytes, chitosan and chondroitin sulfate was self-assembled step-wise onto drug nanoparticles that were prepared by a solvent-evaporation emulsification method using eucalyptol as the oil phase. Four poorly water-soluble model drugs, furosemide, isoxyl, rifampin and paclitaxel were chosen to prepare these particles. Zeta potential, particle size measurements, and microscopic inspection of the coated particles were used to confirm the successful addition of each polyelectrolyte layer and the stability of the nanoparticles. This manufacturing process produced stable drug nanoparticles with volume mean diameters below 250nm. Dissolution tests confirmed that although the nanocoat reduced the dissolution of nanoparticles proportional to the coat thickness; they still dissolved much faster than commercially available micronized powders of the drugs. In addition, increasing the layer thickness (still less than 50nm thick) by adding more LbL bilayers produced sustained release nanoparticles. Ultimately, the LbL nanocoating stabilized these small particles against crystal growth and aggregation in suspension and resulted in nearly perfect controlled drug release.