Continuous-flow production of polymeric micelles in microreactors: Experimental and computational analysis

We report the development of a microfluidic-based process for the production of polymeric micelles (PMs) in continuous-flow microreactors where Pluronie (R) tri-block copolymer is used as model polymeric biomaterial relating to drug delivery applications. A flow focusing configuration is used enabling a controllable, and fast mixing process to assist the formation of polymeric micelles through nanoprecipitation which is triggered by a solvent exchange process when organic solutions of the polymer mixed with a non-solvent. We experientially investigate the effect of polymer concentration, flow rate ratio and microreactor dimension on the PMs size characteristics. The mixing process within the microfluidic reactors is further analyzed by computational modeling in order to understand the hydrodynamic process and its implication for the polymeric micells formation process. The results obtained show that besides the effect of the flow rate ratio, the chemical environment in which the aggregation takes place plays an important role in determining the dimensional characteristics of the produced polymeric micelles. It is demonstrated that microfluidic reactors provide a useful platform for the continuous-flow production of polymeric micelles with improved controllability, reproducibility, and homogeneity of the size characteristics. (C) 2011 Elsevier Inc. All rights reserved.