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

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, B...

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Autores principales:	Ortiz de Solorzano I, Uson L, Larrea A, Miana M, Sebastian V, Arruebo M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Microchannel emulsification high throghput synthesis drug loaded polymer nanoparticles passive mixing numerical modelling Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3c7352eac73c4803a4aed5532bea518c
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spelling	oai:doaj.org-article:3c7352eac73c4803a4aed5532bea518c2021-12-02T00:10:22ZContinuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing1178-2013https://doaj.org/article/3c7352eac73c4803a4aed5532bea518c2016-07-01T00:00:00Zhttps://www.dovepress.com/continuous-synthesis--of-drug-loaded-nanoparticles-using-microchannel--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Isabel 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 modelingOrtiz de Solorzano IUson LLarrea AMiana MSebastian VArruebo MDove Medical PressarticleMicrochannel emulsificationhigh throghput synthesisdrug loaded polymer nanoparticlespassive mixingnumerical modellingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 3397-3416 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microchannel emulsification high throghput synthesis drug loaded polymer nanoparticles passive mixing numerical modelling Medicine (General) R5-920
spellingShingle	Microchannel emulsification high throghput synthesis drug loaded polymer nanoparticles passive mixing numerical modelling Medicine (General) R5-920 Ortiz de Solorzano I Uson L Larrea A Miana M Sebastian V Arruebo M Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing
description	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
format	article
author	Ortiz de Solorzano I Uson L Larrea A Miana M Sebastian V Arruebo M
author_facet	Ortiz de Solorzano I Uson L Larrea A Miana M Sebastian V Arruebo M
author_sort	Ortiz de Solorzano I
title	Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing
title_short	Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing
title_full	Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing
title_fullStr	Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing
title_full_unstemmed	Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing
title_sort	continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/3c7352eac73c4803a4aed5532bea518c
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Continuous synthesis of drug-loaded nanoparticles using microchannel emulsification and numerical modeling: effect of passive mixing

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