Modeling and Simulation of Multiphase Flow for Nanoparticle Translocation

Abstract

The delivery of bioactive compounds is often improved by their encapsulation within systems based on different materials such as polymers and phospholipids. In this regard, one of the most attractive vehicles are liposomes, which can be produced by the self-assembly of phospholipids in aqueous buffered systems. Encapsulation of therapeutic magnetite nanoparticles (MNPs) within liposomes can be accomplished by direct translocation of their lipid bilayer by surface conjugation of potent translocating peptides (and proteins) such as Buforin-II and OmpA. Here, we put forward the notion that to achieve reproducibility and optimize this process, it is possible to develop microfluidic systems that use flow-focusing methods to manipulate the interaction of suspended MNPs (ferrofluids) with the liposomes. With that in mind, we have developed an in silico approach to predict the performance of microfluidic devices specifically designed for the encapsulation process. This was done by running multiphysics simulations in COMSOL to evaluate the macroscopic flow of liposomes and suspended MNPs via a multiphase mixture model. Moreover, we estimated the corresponding interaction using a chemical reaction model based on embedding the Michaelis-Menten equation within the diluted species module's transport. In this case, the enzymes-substrate interaction was considered similar to that of the MNPs-liposome. As a result, we were able to approach saturation kinetics that resembles that obtained experimentally for the uptake of functionalized MNPs. Future work will be directed towards refining the model by considering more details on the possible stages during the interaction of the involved intermediates.

Microfluidics for Multiphase Mixing and Liposomal Encapsulation of Nanobioconjugates: Passive vs. Acoustic Systems

“…Convective conditions were given by the computed laminar velocity field from the mixture model, based on the parametric sweep of inflow velocities for different FRRs. Reaction constants K m and k cat were assigned to 3 mM and 1.245 s −1 , respectively [53].…”