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Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing

Authors Ortiz de Solorzano I, Uson L, Larrea A, Miana M, Sebastian V, Arruebo M

Received 19 March 2016

Accepted for publication 30 April 2016

Published 25 July 2016 Volume 2016:11 Pages 3397—3416

DOI https://doi.org/10.2147/IJN.S108812

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Yashdeep Phanse

Peer reviewer comments 2

Editor who approved publication: Dr Thomas J Webster

Video abstract presented by Isabel Ortiz de Solorzano.

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Isabel Ortiz de Solorzano,1,2,* Laura Uson,1,2,* Ane Larrea,1,2,* Mario Miana,3 Victor Sebastian,1,2 Manuel Arruebo1,2

1Department of Chemical Engineering and Environmental Technologies, Institute of Nanoscience of Aragon (INA), University of Zaragoza, 2CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Centro de Investigación Biomédica en Red, Madrid, 3ITAINNOVA, Instituto Tecnológico de Aragón, Materials & Components, Zaragoza, Spain

*These authors contributed equally to this work


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.

Keywords: microchannel emulsification, high-throughput synthesis, drug-loaded polymer nanoparticles, passive mixing, numerical modeling

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