High Yield and High Loading Preparation of Curcumin–PLGA Nanoparticles Using a Modified Supercritical Antisolvent Technique

Abstract

A modified supercritical antisolvent 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 CO 2 , static agitation, and washing of precipitated particles with supercritical CO 2 . The process stages are continuously repeated until ending injection of a desired amount of solution. The ultrasound operates during the entire process. Poly(lactic-co-glycolic acid) (PLGA) and curcumin are model components. The influences of the process parameters on the yielding and loading are investigated. The maximum yield of the curcumin−PLGA nanoparticles 50 nm in size and the curcumin loading in it reach 96% and 45%, respectively. High yield, high loading, and uniform size are attributed to the efficient mixing between solution droplets and antisolvent, and sequential washing using an antisolvent under ultrasonic agitation. Experimental data are fitted and optimized by neural network simulation.

Nanomaterial Preparation by Extrusion through Nanoporous Membranes

“…. To date, the SCF technique itself has already been used to prepare many nanomaterials including nanoparticles, nanoemulsions, and liposomes . In these studies, SCF can be used either as a solvent for rapid expansion of supercritical solution process or as an antisolvent for supercritical antisolvent process based on the solubility of nanomaterials in SCFs.…”

PLGA–HPMC nanoparticles prepared by a modified supercritical anti-solvent technique for the controlled release of insulin

“…When the pressure was greater than 20 MPa, the size increases greatly (data not shown). This outcome may result from the melting or softening of the polymers and the consequent aggregation of particles [14,16].…”

“…This result can be attributed to the reduction of the density of SC-CO 2 as the temperature increases, reducing the supercritical CO 2 anti-solvent effect. The larger size might be due to the aggregation of particles caused by the softening or melting of polymers at a higher temperature [16]. Additionally, at 45 • C, the insulin solubility in DMSO increases, which counteracts the effect of supercritical CO 2 anti-solvent.…”

“…1, 4 and 11 (Table 1), the particle size decreases when the ultrasonic power increases from 60 W to 240 W, while the loading and yield increase. Increasing the ultrasonic vibration helps the mixing efficiency and prevents aggregation [13,16]. However, power levels greater than 240 W should be avoided to prevent the undesired thermal effects of ultrasonic operation [13].…”

“…Supercritical CO 2 techniques have many advantages in processing, biologics and pharmaceuticals, including their mild process conditions and nontoxicity [2,5,[14][15][16][17][18]. Our previous studies indicated that the modified supercritical anti-solvent technique, which is based on the combination of the batch and continuous modes of supercritical CO 2 anti-solvent techniques, is able to produce solvent-free and uniformly distributed nanoparticles with high loading and yield [16]. This modified method consists of three alternate stages including the partial injection of solution into a precipitation vessel filled with supercritical CO 2 , static agitation, and a brief washing of the precipitated particles with supercritical CO 2 .…”