On the production of chitosan-coated polycaprolactone nanoparticles in a Confined Impinging Jet Reactor

This work is focused on the synthesis of polycaprolactone nanoparticles, coated with chitosan, in... a confined impinging jets reactor using the solvent displacement method. The role of the various reacting species was investigated, evidencing that a biocompatible polymer, e.g. polycaprolactone, is required to support chitosan to obtain a mono-modal particle size distribution, with low particle diameters. A surfactant is required to reduce nanoparticles size (down to a mean diameter of about 260 nm) and obtain a positive Zeta potential (about +31 mV), perfectly suitable for pharmaceutical applications. Different surfactants were tested, and Poloxamer 388 appeared to be preferable to polyvinyl alcohol. The effect of the concentration of Poloxamer 388 (in the range 0.5-5 mg ml-1) and of chitosan (in the range 1.5-5 mg ml-1) on both the mean particle size and on the Zeta potential was also investigated, evidencing that chitosan concentration has the strongest effect on both parameters. Finally, the effect of solvent evaporation, quenching and feed flow rate was investigated, showing that the evaporation stage does not affect particle characteristics, quenching is required to avoid particle aggregation, and a minimum liquid flow rate of 80 ml min-1 is required in the considered reactor to minimize particle size.