High performance hydrodynamic flow focusing platform for the production of PLGA nanoparticles

NICASTRO, ALCIDES; GIORELLO, ANTONELLA; BERLI, CLAUDIO

Congreso; II Brazil?Argentine Microfluidics Congress; 2019

Nanoprecipitation by solvent exchange is a fast and simple technology to prepare polymeric nanoparticles. The process involves dropwise addition of a water-miscible organic polymer solution into a larger quantity of an aqueous non-solvent, under stirring. However, in this bulk approach, phase mixing proceeds slowly and uncontrolled, which favors the formation of hetero-sized nanoparticles and consequently results in an insufficient batch-to-batch consistency [1]. Instead, nanoprecipitation through rapid and controlled microfluidic mixing may enable the formation of more homogeneous polymeric nanoparticles and provide better control of nanoparticle properties such as size and surface characteristics [2].Microfluidics has emerged as alternative technology that offers precisely controlled reaction environments to manufacture polymeric nanoparticles with defined properties and excellent reproducibility [1]. Moreover, hydrodynamic flow focusing has been used for rapid mixing and nanoprecipitation by mixing a water-miscible organic fluid with an aqueous solution. This can provide small nanoparticles with a low polydispersity index [3]. Despite the multitude of innovations in the field of microfluidics, there remains a need for simple setups that can be quickly and inexpensively implemented for the generation and manipulation of flows in microchannels. Existing setups typically rely on expensive syringe or peristaltic pumps that exhibit poor temporal response and instability in fluid delivery, thus limiting their utility in procedures that require precise multiport fluid injection, periodic flow stoppage and scaling-up [4].The aim of this work is the PLGA nanoparticles production through hydrodynamic flow focusing with a pressure-driven control system that enables rapid and precise manipulation of microflows improving the scaling-up manufacture. In the first stage, the flow rate ratios of the aqueous phase and the organic polymer solution were setup by using syringe pumps. The size of nanoparticles was controlled by dynamic light scattering, and the hydrodynamic focusing system was finally optimized. In the second stage, these flow rate ratios are be reproduced employing a pressure-driven control system. The third stage envision a parallelized microfluidic generation of PLGA nanoparticles.References1. Abstiens, K.and Goepferich, A.M. Journal of Drug Delivery Science and Technology, 2019. 49: p. 433-439.2. Karnik, R., Gu, F., Basto, P., Cannizzaro, C., Dean, L., Kyei-Manu, W., Langer, R., and Farokhzad, O.C. Nano Letters, 2008. 8(9): p. 2906-2912.3. Xu, J., Zhang, S., Machado, A., Lecommandoux, S., Sandre, O., Gu, F., and Colin, A. Scientific Reports, 2017. 7(1): p. 4794.4. Bong, K.W., Chapin, S.C., Pregibon, D.C., Baah, D., Floyd-Smith, T.M., and Doyle, P.S. Lab on a Chip, 2011. 11(4): p. 743-747.