On the Scale up of PLA Nanoparticle Production with Impingment Jet Mixing

Biodegradable polymer nanoparticles have the properties necessary to address many of the issues associated with current drug delivery techniques including targeted and controlled delivery.  In this study, the production of poly(lactic acid) (PLA) nanoparticles is investigated using solvent displacement in a batch fed continuous impingement jet mixer, and the effects of system the parameters are examined. Using Pluronic F-127 as the stabilization agent throughout the study, sub-micron PLA “nanoparticles” with diameters ranging from 200 to 250 nm are produced through solvent displacement, and purified and isolated by repeated centrifugation.  The impinging jet mixer (IJM) allows for gram scale particle production. The concentration of surfactant and volume of quench solution is found to have minimal impact on particle diameter; however, the concentration of PLA fed into the IJM is found to significantly impact the particle mean diameter and polydispersity. In addition, we find that excess solvent removal before purifying with centrifugation becomes an important parameter for improved particle yield and redispersibility of the particles after purification because of the larger solvent volumes when scaling up the process.