One of the main routes to ensure that biomolecules or bioactive agents remain active as they are incorporated into products with applications in different industries is by their encapsulation. Liposomes are attractive platforms for encapsulation due to their ease of synthesis and manipulation and the potential to fuse with cell membranes when they are intended for drug delivery applications. We propose encapsulating our recently developed cell-penetrating nanobioconjugates based on magnetite interfaced with translocating proteins and peptides with the purpose of potentiating their cell internalization capabilities even further. To prepare the encapsulates (also known as magnetoliposomes (MLPs)), we introduced a low-cost microfluidic device equipped with a serpentine microchannel to favor the interaction between the liposomes and the nanobioconjugates. The encapsulation performance of the device, operated either passively or in the presence of ultrasound, was evaluated both in silico and experimentally. The in silico analysis was implemented through multiphysics simulations with the software COMSOL Multiphysics 5.5® (COMSOL Inc., Stockholm, Sweden) via both a Eulerian model and a transport of diluted species model. The encapsulation efficiency was determined experimentally, aided by spectrofluorimetry. Encapsulation efficiencies obtained experimentally and in silico approached 80% for the highest flow rate ratios (FRRs). Compared with the passive mixer, the in silico results of the device under acoustic waves led to higher discrepancies with respect to those obtained experimentally. This was attributed to the complexity of the process in such a situation. The obtained MLPs demonstrated successful encapsulation of the nanobioconjugates by both methods with a 36% reduction in size for the ones obtained in the presence of ultrasound. These findings suggest that the proposed serpentine micromixers are well suited to produce MLPs very efficiently and with homogeneous key physichochemical properties.
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.
Endothelialization is required to maintain patency in tissue-engineered vascular grafts (TEVGs). Ligand surface functionalization is intended to induce the adhesion and spreading of Endothelial Cells (ECs). ECs surface adhesion occurs through the integrin-ligand interaction. Here, we propose a chemo-mechanical model, using COMSOL Multiphysics 5.5, to study the optimal ligand distribution in order to improve interaction under laminar blood flow. The proposed model elucidates the role of binding forces and flow velocities over cell spreading as a function of the relevant ligand concentration. This model can contribute to optimizing the surface functionalization of TEVGs for promoting successful endothelialization.
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