Ind. Eng. Chem. Res. 2014, 53, 6569−6574

A modified supercritical anti-solvent method, aiming at high yielding and high loading, is developed for preparation of drug-loaded polymeric nanoparticles. The modified method consists of three alternate stages, injecting solution via a nozzle into a precipitation vessel filled with supercritical CO₂, static agitation, and washing of precipitated particles with supercritical CO₂. The process stages are continuously repeated until ending injection of a desired amount of solution. The ultrasound runs in whole process. PLGA and curcumin are model components. The influences of the process parameters on the yielding and loading are investigated. The maximum yielding of the PLGA-curcumin nanoparticles with the size of 50nm and the curcumin loading in it reaches 96% and 45%, respectively. High yielding, high loading, and uniform size are attributed to the efficient mixing between solution droplets and anti-solvent, and sequential washing using anti-solvent under ultrasonic agitation. Experimental data are fitted and optimized by neural net-work simulation.