Abstract
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.
Highlights
Over the past two decades, microfluidics has gained considerable attention owing to major technological breakthroughs allowing fluid manipulation at sub-millimeter scales for many applications in rapidly developing fields such as biotechnology and biomedical engineering [1]
We were interested in developing an encapsulation strategy for our recently introduced cell-penetrating agents based on magnetite nanoparticles interfaced with translocating peptides and proteins
The selected encapsulating system was liposomes due to their ability to fuse with cell membranes to release cargoes and their ease of synthesis and manipulation
Summary
Over the past two decades, microfluidics has gained considerable attention owing to major technological breakthroughs allowing fluid manipulation at sub-millimeter scales for many applications in rapidly developing fields such as biotechnology and biomedical engineering [1]. In this context, microfluidic systems have permitted the high reproducibility of different processes involving the precise encapsulation of bioactive compounds with unique properties for the potential treatment of several conditions ranging from cancer to neurodegeneration. Due to the ability to manipulate fluid interactions very precisely, microfluidic systems allow the development of droplet-based drug carriers as a result of the interaction between continuous and dispersed phases within highly controlled laminar flows in microchannels. Some of the most studied carriers prepared with this approach include emulsions and liposomes [9,10,11]
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