(483h) Liposomal Encapsulation of Therapeutic Nanobioconjugates Enabled By Microfluidic Devices: In silico Analysis Via Comsol Multiphysics
AIChE Annual Meeting
Thursday, November 19, 2020 - 9:45am to 10:00am
This work is therefore dedicated to designing microfluidic devices for the liposomal encapsulation of our therapeutic nanobioconjugates. We designed microfluidic devices and tested them in silico with the aid of COMSOL. In our first approach, we put in contact a ferrofluid containing the nanobioconjugates with a suspension of the liposomes in isopropyl alcohol. This interaction was simulated by applying a mixture model for the ferrofluid motion, which was coupled to a convection-diffusion model of diluted species for the mixing with the liposome suspension. Figure 1 shows the results for the flow of the dispersed phase in the microfluidic device. The dispersed phase achieves a complete mixing with the continuous aqueous phase when it arrives at the second loop after about 15 seconds. This is followed by a regime where of a constant volume fraction of around 0.2 under laminar conditions after 30 seconds. Figure 2 illustrates the concentration fraction of the ferrofluid as it mixes with the liposomesâ suspension. As for the dispersed phase in Figure 1, complete mixing is achieved when the fluids reach the second loop of the mixing chamber. As a result, we are certain that the loops of the serpentine chamber contribute to the interaction between both fluids and allow a uniform mixing pattern within a few seconds. To some extent, this can be explained by the effect of Dean vortices inducing chaotic advection .
Alternatively, we decided to explore the possibility of increasing the chances for encapsulation by subjecting the device to an acoustic field, which will be generated by an ultrasonic bath in a subsequent experimental testing stage. In this context, ultrasound is used as an external energy source capable of altering the mixing and promoting interactions through acoustic streaming . This new in silico study builds upon the two previously coupled modules by adding an acoustics model with ultrasonic frequencies in the range of 20 kHz-42 kHz. Both studies are applied for the designed Y-type micromixer (inlets angle of 45°) with a serpentine mixing chamber (see Figure 2).
Figures 3a and 3b show the 2D surface sound pressure and acoustic pressure field of ultrasound in the presence of the designed microfluidic device. The same fields in the absence of the microfluidic device are shown in Figures 4a and 4b. Figure 4c shows the changes in both the acoustic field pressure and sound pressure level when the microfluidic device is immersed in the ultrasonic bath. This shows transmission and reflection of the incident ultrasound waves generated by the acoustic field after they impact the solid structure material of the microfluidic device, which was built in COMSOL by using the properties of polymethyl methacrylate (PMMA). This will be the actual situation as we have perfected a low-cost manufacturing technique that is based on laser cutting and engraving on PMMA sheets.
Based on the results obtained thus far, our current ongoing work focuses on coupling the mixture model, transport of diluted species and pressure acoustics. This with the purpose of estimating whether the ultrasonic vibration facilitates encapsulation. Finally, details of the encapsulation process will be attempted by modeling the translocation of the ferrofluid through the lipid bilayer of liposomes after setting up their boundaries as reactive interfaces. For this model, optimal values for relevant parameters such as the velocity field and concentrations can be obtained from previous simulations and subsequently introduced into this multiphysics study.
 T. Alkayyali, T. Cameron, B. Haltli, R. G. Kerr, and A. Ahmadi, âAnalytica Chimica Acta Micro fl uidic and cross-linking methods for encapsulation of living cells and bacteria - A review,â Anal. Chim. Acta, vol. 1053, pp. 1â21, 2019.
 T. P. Lagus and J. F. Edd, âA review of the theory , methods and recent applications of high-throughput single-cell droplet microfluidics,â 2013.
 A. D. Stroock et al., âChaotic Mixer for Microchannels,â vol. 647, no. 2002, 2012.
 D. Screening, âMicrofluidic Devices for Drug Delivery Systems and Drug Screening,â 2018.
 W. Gao and Y. Chen, âInternational Journal of Heat and Mass Transfer Microencapsulation of solid cores to prepare double emulsion droplets by microfluidics,â Int. J. Heat Mass Transf., vol. 135, pp. 158â163, 2019.
 L. Sercombe, T. Veerati, F. Moheimani, S. Y. Wu, A. K. Sood, and S. Hua, âAdvances and challenges of liposome assisted drug delivery,â Front. Pharmacol., vol. 6, no. DEC, pp. 1â13, 2015.
 A. Nagayasu, K. Uchiyama, and H. Kiwada, âThe size of liposomes: A factor which affects their targeting efficiency to tumors and therapeutic activity of liposomal antitumor drugs,â Adv. Drug Deliv. Rev., vol. 40, no. 1â2, pp. 75â87, 1999.
 J. S. Kim, âLiposomal drug delivery system,â J. Pharm. Investig., vol. 46, no. 4, pp. 387â392, 2016.
 G. Bozzuto and A. Molinari, âLiposomes as nanomedical devices,â Int. J. Nanomedicine, vol. 10, pp. 975â999, 2015.
 M. Maeki, N. Kimura, Y. Sato, H. Harashima, and M. Tokeshi, âAdvances in micro fl uidics for lipid nanoparticles and extracellular vesicles and applications in drug delivery systems â,â Adv. Drug Deliv. Rev., vol. 128, pp. 84â100, 2018.
 J. Gubernator, âActive methods of drug loading into liposomes: Recent strategies for stable drug entrapment and increased in vivo activity,â Expert Opin. Drug Deliv., vol. 8, no. 5, pp. 565â580, 2011.
 N. Pamme, âContinuous flow separations in microfluidic devices,â Lab Chip, vol. 7, no. 12, pp. 1644â1659, 2007.
 A. J. Conde et al., âContinuous flow generation of magnetoliposomes in a low-cost portable microfluidic platform,â Lab Chip, vol. 14, no. 23, pp. 4506â4512, 2014.
 M. GuimarÃ£es, S. Correia, M. L. Briuglia, F. Niosi, and D. A. Lamprou, âMicro fl uidic manufacturing of phospholipid nanoparticles : Stability , encapsulation ef fi cacy , and drug release,â vol. 516, pp. 91â99, 2017.
 M. Cuellar et al., âNovel BUF2-magnetite nanobioconjugates with cell-penetrating abilities,â Int. J. Nanomedicine, vol. 13, pp. 8087â8094, 2018.
 N. Lopez-Barbosa et al., âMagnetite-OmpA Nanobioconjugates as Cell-Penetrating Vehicles with Endosomal Escape Abilities,â ACS Biomater. Sci. Eng., vol. 6, no. 1, pp. 415â424, 2020.
 J. Perez, J. Cifuentes, M. Cuellar, A. Suarez-Arnedo, J. C. Cruz, and C. MuÃ±oz-Camargo, âCell-penetrating and antibacterial BUF-II nanobioconjugates: Enhanced potency via immobilization on polyetheramine-modified magnetite nanoparticles,â Int. J. Nanomedicine, vol. 14, pp. 8483â8497, 2019.
 E. Sollier, H. Amini, D. E. Go, P. A. Sandoz, K. Owsley, and D. Di Carlo, âInertial microfluidic programming of microparticle-laden flows for solution transfer around cells and particles,â Microfluid. Nanofluidics, vol. 19, no. 1, pp. 53â65, 2015.
This paper has an Extended Abstract file available; you must purchase the conference proceedings to access it.
Do you already own this?
Log In for instructions on accessing this content.
|AIChE Emeritus Members||$105.00|
|AIChE Graduate Student Members||Free|
|AIChE Undergraduate Student Members||Free|