Solvent impact on polymer nanoparticles prepared nanoprecipitation

Polymer nanoparticles, relevant for e.g., drug vectorization, can be prepared by means of nanoprecipitation, a convenient one-step manufacturing process strikingly different from well-established emulsification-based techniques. The current study elucidates the paramount effect of the utilized organic solvent on the size properties of particles generated during nanoprecipitation in a systematic manner. When poly(vinyl acetate) was dissolved in a "homologous" series of water-miscible, aliphatic alcohols (i.e., methanol, ethanol, 1- and 2-propanol and tert-butanol) and then precipitated in water, the size of the obtained nanoparticles depended on (1) the polymer concentration in organic solution and (2) the utilized organic solvent (rank order: methanol < ethanol < 1-propanol approximate to 2-propanol < tert-butanol). A higher polymer concentration in the organic phase led to larger nanoparticles. The choice of the current organic solvent "library" allowed for a systematic change of solvent/non-solvent exchange ratios, solvent/water and polymer/solvent interaction parameters, which all correlated well with the final particle size distribution. A smaller exchange ratio and a lower solvent/ water interaction value were associated with more intensive mixing effects and, thus, smaller polymer nanoparticles were formed. A lower polymer/solvent interaction parameter, an indication for more unfolded polymer chains in a given organic solvent, led to larger colloidal particles. Overall, nanoprecipitation is a relevant tool for the fabrication of polymer-based colloidal drug delivery vehicles. In contrast to previous studies, which pursued a "random" selection of organic solvents, this research utilized a systematic approach to mechanistically underline the outstanding impact of organic solvent quality on the size properties of the obtained polymer nanoparticles, which, thus, is highly relevant for the field of nanomedicine.