title: Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing.
abstract: By using interdigital microfluidic reactors, monodisperse poly(d,l lactic-co-glycolic acid) nanoparticles (NPs) can be produced in a continuous manner and at a large scale (~10 g/h). An optimized synthesis protocol was obtained by selecting the appropriated passive mixer and fluid flow conditions to produce monodisperse NPs. A reduced NP polydispersity was obtained when using the microfluidic platform compared with the one obtained with NPs produced in a conventional discontinuous batch reactor. Cyclosporin, an immunosuppressant drug, was used as a model to validate the efficiency of the microfluidic platform to produce drug-loaded monodisperse poly(d,l lactic-co-glycolic acid) NPs. The influence of the mixer geometries and temperatures were analyzed, and the experimental results were corroborated by using computational fluid dynamic three-dimensional simulations. Flow patterns, mixing times, and mixing efficiencies were calculated, and the model supported with experimental results. The progress of mixing in the interdigital mixer was quantified by using the volume fractions of the organic and aqueous phases used during the emulsification-evaporation process. The developed model and methods were applied to determine the required time for achieving a complete mixing in each microreactor at different fluid flow conditions, temperatures, and mixing rates.
authors.affiliation: Department of Chemical Engineering and Environmental Technologies, Institute of Nanoscience of Aragon (INA), University of Zaragoza; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigación Biomédica en Red, Madrid.
authors.forename: Isabel
authors.initials: I
authors.lastname: Ortiz de Solorzano
authors.affiliation: Department of Chemical Engineering and Environmental Technologies, Institute of Nanoscience of Aragon (INA), University of Zaragoza; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigación Biomédica en Red, Madrid.
authors.forename: Laura
authors.initials: L
authors.lastname: Uson
authors.affiliation: Department of Chemical Engineering and Environmental Technologies, Institute of Nanoscience of Aragon (INA), University of Zaragoza; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigación Biomédica en Red, Madrid.
authors.forename: Ane
authors.initials: A
authors.lastname: Larrea
authors.affiliation: ITAINNOVA, Instituto Tecnológico de Aragón, Materials & Components, Zaragoza, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Miana
authors.affiliation: Department of Chemical Engineering and Environmental Technologies, Institute of Nanoscience of Aragon (INA), University of Zaragoza; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigación Biomédica en Red, Madrid.
authors.forename: Victor
authors.initials: V
authors.lastname: Sebastian
authors.affiliation: Department of Chemical Engineering and Environmental Technologies, Institute of Nanoscience of Aragon (INA), University of Zaragoza; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigación Biomédica en Red, Madrid.
authors.forename: Manuel
authors.initials: M
authors.lastname: Arruebo
mesh_terms: D003198:Computer Simulation; D016572:Cyclosporine / Q000494:pharmacology; D004655:Emulsions / Q000737:chemistry*; D057446:Hydrodynamics; D019344:Lactic Acid / Q000737:chemistry; D044085:Microfluidics; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009716:Numerical Analysis, Computer-Assisted; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D004655:Emulsions; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016572:Cyclosporine
keywords: drug-loaded polymer nanoparticles; high-throughput synthesis; microchannel emulsification; numerical modeling; passive mixing