Use of microreactors and freeze-drying in the manufacturing process of chitosan coated PCL nanoparticles

This paper is focused on the synthesis of chitosan-coated polycaprolactone nanoparticles in microreactors and on the freeze-drying of the nanosuspension, to separate the particles from the liquid phase. Nanoparticles were produced in the confined impinging jets mixer (CIJM) and in the multi-inlet vortex mixer (MIVM), using the solvent displacement method, with acetone or tert-butanol (TBA) as polymer solvent. The study was initially carried out considering a feed flow rate of 80 ml min-1: using acetone, the mean particle size was lower (163 +/- 7 nm) and the Zeta potential was higher (31.4 +/- 37 mV) with the MIVM, with respect to the CIJM (265 +/- 31 nm and 9.8 +/- 2.4 mV, respectively). Slightly larger particles were obtained using TBA in the MIVM (mean diameter: 221 +/- 44 nm): in this case it is no longer required removing the solvent before the freezedrying stage. The effect of the liquid flow rate was then investigated, confirming that the best results were obtained at 80 ml min-1. With respect to the freeze-drying process, the effect of lyoprotectants and of steric stabilizers on particle stability was investigated. Best results were obtained with 5% sucrose and 2.5% Poloxamer 388 (mean diameter: 306 +/- 8 nm); in all cases Zeta potential remained positive and larger than + 30 mV. Preliminary results about the encapsulation of a test drug, ciprofloxacin, are also shown and discussed.