Please login first
Modelling and simulation of multiphase flow for nanoparticle translocation
* 1, 2 , 1 , 1 , 1 , 3 , 4
1  Department of Biomedical Engineering, Universidad de los Andes, Bogotá, Colombia, Cra. 1E No. 19a – 40, Bogotá, DC 111711
2  School of Chemical Engineering and Advanced Materials, The University of Adelaide, South Australia 5005, Australia
3  Department of Chemical and Food Engineering, Universidad de los Andes, Bogotá, Colombia, Cra. 1E No. 19a – 40, Bogotá, DC 111711, Colombia
4  Department of Electric and Electronics Engineering, Universidad de los Andes, Bogotá, Colombia, Cra. 1E No. 19a – 40, Bogotá, DC 111711, Colombia

Abstract:

Encapsulation of bioactive molecules within liposomes represents a potential approach for
upholding their activity and stability under harsh environments [1]. Indeed, liposomes are
considered one of the most attractive vehicles to deliver therapeutics [2-4]. Magnetite nanoparticles
(MNPs) linked to molecules such as OmpA and Buforin-II are promising to enhance translocation of
those compounds through the lipid bilayer of liposomes and consequently, of cells [5-7]. Besides,
microfluidic devices have shown to be successful at producing homogeneous and stable liposomes
by controlling the interaction of continuous and dispersed phases [8-12]. This work intends to
analyze multiphase behavior under external forces in microfluidic devices for encapsulating
ferrofluidic compounds that model MNPs transported into liposomes to optimize the use of these
devices. In ongoing work, we have developed in silico models, which suggest that by introducing
acoustic fields from ultrasonic baths, the interaction between continuous and dispersed phases
increases. This is mainly due to acoustophoretic forces inducing a multidirectional force vector within
microfluidic channels, which serves to focus fluid streamlines, enhances mixing, and ultimately
allows the transport of nanoparticles [13-14]. Regarding this, to quantify the interaction between
fluid phases, which relates the encapsulation process of the nanoparticles within liposomes, we
propose a reaction model that couples mixture, diluted species, and chemical reactions. This
approach considers Michaelis-Menten equation to model the interaction between the liposomes and
nanoparticles, referring to enzyme and substrate respectively. These models are implemented aided
by COMSOL Multiphysics® software. Correlating both reaction and mixture behavior it is expected
to estimate the efficiency of the proposed method, by quantifying changes in the dispersed phase
fraction and the reaction rate, which represents the active pass through the bilayer.

[1] T. Alkayyali, T. Cameron, B. Haltli, R. G. Kerr, and A. Ahmadi, “Microfluidic and cross-linking
methods for encapsulation of living cells and bacteria - A review,” Anal. Chim. Acta, vol. 1053, pp.
1–21, 2019.
[2] M. Maeki, N. Kimura, Y. Sato, H. Harashima, and M. Tokeshi, “Advances in microfluidics for lipid
nanoparticles and extracellular vesicles and applications in drug delivery systems”, Adv. Drug Deliv.
Rev., vol. 128, pp. 84–100, 2018.
[3] L. Sercombe, T. Veerati, F. Moheimani, S. Y. Wu, A. K. Sood, and S. Hua, “Advances and
challenges of liposome assisted drug delivery,” Front. Pharmacol., vol. 6, no. DEC, pp. 1–13, 2015.
[4] A. Akbarzadeh et al., “Liposome: Classification, preparation, and applications,” Nanoscale Res.
Lett., vol. 8, no. 1, pp. 1–8, 2013.
[5] N. Lopez-Barbosa et al., “Magnetite-OmpA Nanobioconjugates as Cell-Penetrating Vehicles with
Endosomal Escape Abilities,” ACS Biomater. Sci. Eng., vol. 6, no. 1, pp. 415–424, 2020.
[6] M. Cuellar et al., “Novel BUF2-magnetite nanobioconjugates with cell-penetrating abilities,” Int.
J. Nanomedicine, vol. 13, pp. 8087–8094, 2018.
[7] J. Perez, J. Cifuentes, M. Cuellar, A. Suarez-Arnedo, J. C. Cruz, and C. Muñoz-Camargo, “Cellpenetrating and antibacterial BUF-II nanobioconjugates: Enhanced potency via immobilization on
polyetheramine-modified magnetite nanoparticles,” Int. J. Nanomedicine, vol. 14, pp. 8483–8497,
2019.
[8] S. Damiati, U. Kompella, S. Damiati, and R. Kodzius, “Microfluidic Devices for Drug Delivery
Systems and Drug Screening,” Genes (Basel)., vol. 9, no. 2, p. 103, 2018.
[9] L. M. Montes-de-Oca et al., “Micro-Encapsulation of Probiotic Metabolites and Magnetic
Nanoparticles Inside Liposomes using Microfluidic Devices,” Microsc. Microanal., vol. 24, no. S1, pp.
1430–1431, 2018.
[10] J. Gubernator, “Active methods of drug loading into liposomes: Recent strategies for stable drug
entrapment and increased in vivo activity,” Expert Opin. Drug Deliv., vol. 8, no. 5, pp. 565–580, 2011.
[11] M. Guimarães Sá Correia, M. L. Briuglia, F. Niosi, and D. A. Lamprou, “Microfluidic
manufacturing of phospholipid nanoparticles: Stability, encapsulation efficacy, and drug release,”
Int. J. Pharm., vol. 516, no. 1–2, pp. 91–99, 2017.
[12] A. J. Conde et al., “Continuous flow generation of magnetoliposomes in a low-cost portable
microfluidic platform,” Lab Chip, vol. 14, no. 23, pp. 4506–4512, 2014.
[13] D. J. Collins, Z. Ma, J. Han, and Y. Ai, “Continuous micro-vortex-based nanoparticle
manipulation via focused surface acoustic waves,” Lab Chip, vol. 17, no. 1, pp. 91–103, 2017.
[14] G. G. Yaralioglu, I. O. Wygant, T. C. Marentis, and B. T. Khuri-Yakub, “Ultrasonic mixing in
microfluidic channels using integrated transducers,” Anal. Chem., vol. 76, no. 13, pp. 3694–3698,
2004.

Keywords: liposomes; nanoparticles; in silico study; multiphase; microfluidics; acoustophoresis; translocation
Top