Millifluidic Synthesis Of Protein Loaded Nanocapsules

Nanocapsules,a protein delivery platform,have attracted much attention due to their enhanced therapeutic efficacy and good biocompatibility.After increasing the scale of production,however,traditional production techniques of nanocapsules are not quite suitable when pursing high protein loaded efficiency and uniformity of the nanocapsules due to their existing difficulties in homogeneously mixing raw materials and heat transfer.The protein loaded nanocapsules synthesized by in situ free-radical polymerization showed effective therapeutic effect by the traditional stirring method.Herein,to solve the problem existing in the bulk mixing method,we report a simple way to produce nanocapsules using our designed millifluidic device.The synthesized nanocapsules were mainly characterized by dynamic light scattering(DLS),transmission electron microscopy(TEM)and agarose gel electrophoresis and so on.Then protein loaded efficiency as well as uniformity of the nanocapsules were synthesized by millifluidic mixing.Biocompatibility of these nanocapsules was also verified via cytocompatibility,acute toxicity test,blood compatibility assay,skin stimulation test,vascular stimulation test,and allergic test.The results showed that the nanocapsules synthesized by our designed millifluidic device are about 18 nm in size,and have higher protein loaded efficiency as well as narrower size distribution compared with those synthesized by commonly used bulk mixing method.Besides,these nanocapsules can well ensure the functions of their inner protein and have high biocompatibility.The cell viability was above 90%.The results of acute toxicity,hemolysis,skin irritation,vascular irritation and allergy showed that these nanocapsules have high biocompatibility.In all,by using our designed millifluidic device,we provide an alternative way to synthesize high quality nanocapsules.