| Autor: |
López RR; Department of Electrical Engineering, École de technologie supérieure, 1100 Notre Dame West, Montreal, Quebec H3C 1K3, Canada.; Cancer Research Program, RI-MUHC, McGill University, 1001 Decarie Boulevard, Montreal, Quebec H4A 3J1, Canada., Ocampo I; School of Engineering and Sciences, Tecnológico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, Tecnológico Monterrey, N.L., Monterrey 64849, Mexico., Font de Rubinat PG; Department of Electrical Engineering, ETS d'Enginyeria Industrial de Barcelona, Universitat Politècnica de Catalunya, 647 Avinguda Diagonal, Catalunya, Barcelona 08028, Spain., Sánchez LM; Department of Engineering, Universidad Autónoma de Querétaro, Cerro de las Campanas s/n, Qro., Santiago de Querétaro 76010, Mexico., Alazzam A; Department of Electrical Engineering, École de technologie supérieure, 1100 Notre Dame West, Montreal, Quebec H3C 1K3, Canada.; System on Chip Center, Department of Mechanical Engineering, Khalifa University, Abu Dhabi 127788, United Arab Emirates., Tsering T; Cancer Research Program, RI-MUHC, McGill University, 1001 Decarie Boulevard, Montreal, Quebec H4A 3J1, Canada., Bergeron KF; Centre de Recherche sur Les Maladies Orphelines (CERMO-FC), Département des Sciences Biologiques, Université du Québec à Montréal, 141 Président-Kennedy, Montréal, Québec H2X 1Y4, Canada., Camacho-Léon S; School of Engineering and Sciences, Tecnológico de Monterrey, Av. Eugenio Garza Sada 2501 Sur, Tecnológico Monterrey, N.L., Monterrey 64849, Mexico., Burnier JV; Cancer Research Program, RI-MUHC, McGill University, 1001 Decarie Boulevard, Montreal, Quebec H4A 3J1, Canada., Mounier C; Centre de Recherche sur Les Maladies Orphelines (CERMO-FC), Département des Sciences Biologiques, Université du Québec à Montréal, 141 Président-Kennedy, Montréal, Québec H2X 1Y4, Canada., Stiharu I; Department of Mechanical, Industrial and Aerospace Engineering, Concordia University, 1455 de Maisonneuve Blvd. West, Montreal, Quebec H3G 1M8, Canada., Nerguizian V; Department of Electrical Engineering, École de technologie supérieure, 1100 Notre Dame West, Montreal, Quebec H3C 1K3, Canada. |
| Abstrakt: |
Liposomes encapsulate different substances ranging from drugs to genes. Control over the average size and size distribution of these nanoparticles is vital for biomedical applications since these characteristics determine to a high degree where liposomes will accumulate in the human body. Micromixers enable the continuous flow synthesis of liposomes, improving size control and reproducibility. Recently, Dean flow dynamics-based micromixers, such as the periodic disturbance mixer (PDM), have been shown to produce controlled-size liposomes in a scalable and reproducible way. However, contrary to micromixers based on molecular diffusion or chaotic advection, their production factors and their influence over liposome properties have not yet been addressed thoroughly. In this work, we present a comprehensive parametric study of the effects of flow conditions and molecular changing factors such as concentration, lipid type, and temperature on the physicochemical characteristics of liposomes. Numerical models and confocal images are used to quantitatively and qualitatively evaluate mixing performance under different liposome production conditions and their relationship with vesicle properties. The total flow rate (TFR) and, to a lesser extent, the flow rate ratio (FRR) control the liposome size and size distribution. Effects on liposome size are also observed by changing the molecular factors. Moreover, the liposome ζ potential is independent of the factors studied here. The micromixer presented in this work enables the production of liposomes as small as 24 nm, with monodispersed to low or close to low polydispersed liposome populations as well as a production rate as high as 41 mg/h. |
