(511g) Influence of mixing on nanoparticle size distribution

Polymer nanoparticles have been widely used as carriers for encapsulated hydrophobic drug molecules. Such drug delivery nanocarriers provide therapeutic efficacy by overcoming biological barriers and improving circulation time in the body. Nanoparticle size and particle size distribution affected by process synthesis conditions play a crucial role in determining therapeutic efficacy. Polymer nanoparticles synthesized through common nanoprecipitation techniques undergo rapid self-assembly in milliseconds. However, the mixing process in large batch reactors is accomplished in the order of minutes. This difference between the polymer self-assembly time and reactor mixing time results in a broad distribution of nanoparticles, with a high polydispersity. A polydisperse nanoparticle distribution compromises the uniformity of size-dependent properties, undesired for drug delivery applications. Hence, the goal is to achieve a reactor mixing time equivalent to the polymer self-assembly timescale. It is difficult to achieve rapid mixing in large-scale reactor vessels. Thus, microreactor designs such as T-mixer, Y-mixer, and confined impinging jet mixer have been used for polymer nanoparticles synthesis. Such dual inlet microreactors designs fail to achieve effective mixing under asymmetric flow conditions, i.e., when the flow rates of two inlets are unequal. This significantly restricts exploration of reaction parameters, such as supersaturation achieved in nanoprecipitation and limits applicability for processes involving expensive reagents, such as drugs. Our strategy involves decreasing the reactor length scale to allow for a smaller reactor volume and thus, achieve rapid mixing while being capable of operating under asymmetric flow conditions. Here, we present a three-inlet microreactor (also known as the Jet mixing reactor, JMR) that comprises two oppositely placed fluid streams that orthogonally impinge on a single fluid stream, developing vortexes and achieving rapid mixing in milliseconds. The proposed JMR resembles a cross-flow geometry and has the size of a dollar coin with inlet diameters ranging from 0.5-1 mm. As polymer nanoprecipitation kinetics is strongly affected by mixing inside the reactor, it is imperative to characterize mixing in the JMR. Mixing in the JMR was characterized using a competitive chemical reaction set, known as the Villermaux-Dushman reaction. Mixing dependence on different factors was explored, including dependence on inlet fluid stream flow rates, fluid viscosity, and cross-flow fluid ratios. Flow dynamics were also visualized using computational fluid dynamics with simulations on the COMSOL software. The competitiveness of JMR over conventional large batch vessels was assessed through model nanoparticle (Polylactic acid-co-glycolic acid, PLGA) synthesis, with nanoparticle size and particle size distribution serving as an evaluation criterion.