A focus of the nanoprecipitation by solvent displacement: example of poly(MAOTIB) intended to in vivo applications

Abstract

Through this study, we propose to specifically focus on a particular stage of the fabrication of polymeric nanoparticles intended to be used as contrast agent for biomedical X-ray imaging. These nanoparticles, made from nanoprecipitation of preformed polymer, poly(MAOTIB) (poly(2-methacryloyloxyethyl(2,3,5-triiodobenzoate))) follow a solvent displacement process. This method, widely used in literature, is sensitive to the formulation and process parameters such as nature and concentrations of surfactant and polymer, solvent / non-solvent ratio, rate of addition of one phase in the other one, respective volumes of the phase, and homogenization shearing rate. On the other hand, in function of the aimed administration route, the final suspension should obey to specific constraints on final product, e.g. size range and polydispersity, final particle concentration (i.e. iodine concentration) and surfactant concentration. In the present work, we report a specific investigation on the nanoprecipiation of poly(MAOTIB) in tetrahydrofuran, dropped in water or ethanol (as non-solvent) and stabilized by nonionic surfactant. The objective is to show and explain the potentials and limitations of such the process, but also to provide a guidance on the way to optimize it.