Size control in production and freeze-drying of poly-ε-caprolactone nanoparticles.

This work is focused on the control of poly-ε-caprolactone nanoparticle characteristics, notably size and size distribution, in both the production and preservation (by using freeze-drying) stages. Nanoparticles were obtained by employing the solvent displacement method in a confined impinging jets mixer. The effect of several operating conditions, namely, initial polymer concentration and solvent-to-antisolvent flow rate ratio, and the influence of postprocessing conditions, such as final dilution and solvent evaporation, on nanoparticle characteristics was investigated. Further addition of antisolvent (water) after preparation was demonstrated to be effective in obtaining stable nanoparticles, that is, avoiding aggregation that would result in larger particles. On the contrary, solvent (acetone) evaporation was shown to have a small effect on the final nanoparticle characteristics. Eventually, freeze-drying of the solutions containing nanoparticles, after solvent evaporation, was also investigated. To ensure maximum nanoparticles stability, lyoprotectants (e.g., sucrose and mannitol) and steric stabilizers (e.g., Cremophor EL and Poloxamer 388) had to be added to the suspensions. The efficacy of the selected lyoprotectants, in the presence (or absence) of steric stabilizers, and in various concentrations, to avoid particle aggregation during the freeze-drying process was investigated, thus pointing to the optimal formulation.