Ciprofloxacin (CIP) has been widely used to treat many types of bacterial infections. Herein, we reported a green approach for preparation of CIP nanoparticles via solvent anti-solvent precipitation by using subcritical water ethanol mixture as the solvent. The solubility of CIP in subcritical water-ethanol mixture (with various ethanol ratio of 0, 5, and 20 wt%) at the temperature range from 100 degrees C to 170 degrees C and constant pressure of 4 MPa were measured. The chemical structure of CIP was stable after processed in subcritical water-ethanol mixture at up to 170 degrees C, confirmed by Fourier transformed infrared analysis. The obtained solubility data of CIP were correlated using a modified Apelblat model and the results of the predicted solubility show good agreement with the experimental value. The nanonization of CIP via solvent anti-solvent precipitation process that used the tunable solvent power of subcritical water-ethanol mixture was conducted. Two kinds of no-ionic, hydrophilic polymer, including polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG), were introduced as stabilizers in the precipitation process to obtain CIP nanoparticle with improved dissolution rate. These results show that as-synthesized CIP nanoparticles are promising for oral administration of CIP drugs. (C) 2017 Elsevier B.V. All rights reserved.