@article{55375a0aa1b743fd8b4c618494c78cb2,
title = "Surface response based modeling of liposome characteristics in a periodic disturbance mixer",
abstract = "Liposomes nanoparticles (LNPs) are vesicles that encapsulate drugs, genes, and imaging labels for advanced delivery applications. Control and tuning liposome physicochemical characteristics such as size, size distribution, and zeta potential are crucial for their functionality. Liposome production using micromixers has shown better control over liposome characteristics compared with classical approaches. In this work, we used our own designed and fabricated Periodic Disturbance Micromixer (PDM). We used Design of Experiments (DoE) and Response Surface Methodology (RSM) to statistically model the relationship between the Total Flow Rate (TFR) and Flow Rate Ratio (FRR) and the resulting liposomes physicochemical characteristics. TFR and FRR effectively control liposome size in the range from 52 nm to 200 nm. In contrast, no significant effect was observed for the TFR on the liposomes Polydispersity Index (PDI); conversely, FRR around 2.6 was found to be a threshold between highly monodisperse and low polydispersed populations. Moreover, it was shown that the zeta potential is independent of TFR and FRR. The developed model presented on the paper enables to pre-establish the experimental conditions under which LNPs would likely be produced within a specified size range. Hence, the model utility was demonstrated by showing that LNPs were produced under such conditions.",
keywords = "Continuous-flow synthesis, Liposomes, Microfluidics, Micromixers, Nanoparticles",
author = "L{\'o}pez, {Rub{\'e}n R.} and Ixchel Ocampo and S{\'a}nchez, {Luz Mar{\'i}a} and Anas Alazzam and Bergeron, {Karl F.} and Sergio Camacho-Le{\'o}n and Catherine Mounier and Ion Stiharu and Vah{\'e} Nerguizian",
note = "Funding Information: This research was funded by CONACyT-ETS (389081), CONACyT international mobility (859557), NSERC (REN253), Khalifa University (CIRA-2019-014), and {\'E}TS. This work was supported by the grant CONACyT-ETS, CONACyT International Mobility Scholarship, Concordia University, NSREC, {\'E}cole de technologie sup{\'e}rieure, Khalifa University, and UQAM. CMC Microsystems supported this work through lending equipment and software. We would like to acknowledge the chemical department at UQAM, the NANOQAM, and COFAMIQ network for the training in the cleanroom, nanoparticle characterization, and equipment use. Especially to Ricardo Izquierdo, Alexandre Robichaud, Galyna Shul, Jacqueline Hue Tieu, and Luc Arsenault. Nanoparticle Tracking Analysis was performed in collaboration with Janusz Rak, Miguel Burnier and Julia Burnier Laboratory at McGill University Health Centre under the supervision of Laura Montermini and Thupten Tsering. Paula Gonzalez from Universitat Polit{\`e}cnica de Catalunya supported mixing imaging experiments. Prasun Lala from SARA Group {\'E}TS helped to proofread this article. Funding Information: FunFduinndgi:ngT:h Tishirse sreesaeracrhchw wasasf ufunnddeeddb byy CCOONNAACCyyTT‐-EETTSS ((338899008811),) ,CCOONNAACCyTy Tinitnertnerantiaotnioaln malombiolibtyil i(t8y59(585579)5, 57), NSENRSCER(CR E(RNE2N5325),3K), hKahliaflaifaU Uninvievresristiyty( C(CIRIRAA-‐22001199-‐001144)),, aanndd {\'E}{\'E}TTSS.. Acknowledgments: This work was supported by the grant CONACyT-ETS, CONACyT International Mobility Scholarship, Concordia University, NSREC, {\'E}cole de technologie sup{\'e}rieure, Khalifa University, and UQAM. CMC Microsystems supported this work through lending equipment and software. We would like to acknowledge the chemical department at UQAM, the NANOQAM, and COFAMIQ network for the training in the cleanroom, nanoparticle characterization, and equipment use. Especially to Ricardo Izquierdo, Alexandre Robichaud, Galyna Shul, Jacqueline Hue Tieu, and Luc Arsenault. Nanoparticle Tracking Analysis was performed in collaboration with Janusz Rak, Miguel Burnier and Julia Burnier Laboratory at McGill University Health Centre under the supervision of Laura Montermini and Thupten Tsering. Paula Gonzalez from Universitat Polit{\`e}cnica de Catalunya supported mixing imaging experiments. Prasun Lala from SARA Group {\'E}TS helped to proofread this article. Publisher Copyright: {\textcopyright} 2020 by the authors.",
year = "2020",
month = mar,
day = "1",
doi = "10.3390/mi11030235",
language = "British English",
volume = "11",
journal = "Micromachines",
issn = "2072-666X",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "3",
}