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In this work, we describe a hydrodynamic flow-focusing microfluidic process to produce stealth cationic liposomes (SCL), stabilized with poly(ethylene glycol) (PEG), with uniform and reproducible features. Through cryogenic transmission electron microscopy (cryo-TEM) characterization and real-time monitoring, we verified the formation of multi-sized lipid self-aggregates, which can be attributed to micelles formation. These structures tend to undergo deposition within the PDMS/glass microchannels through intermolecular interactions with the glass walls, hindering not only the process reproducibility but also the final biological application of the SCL products. In view of this, we propose the modulation of ionic strength of the side streams aiming to ionically shield the glass surface, decrease the intermolecular interactions of the lipid polar heads, and, essentially, to promote the bilayer-driven self-assembly of SCL with 1% of DSPE-PEG lipid. Herein, we applied phosphate-buffered saline (PBS) from 10 to 50 mM concentration as side streams, and evaluated its effects on SCL final physicochemical properties in terms of size distribution, mean diameter, zeta potential and polydispersity index (PDI). We present evidences indicating that the ionic strength can be used as a microfluidic process parameter to modulate the lipids self-assembly kinetics whilst preventing micelles formation. Finally, the proposed diffusion-based microfluidic system with high ionic strength enables the formation of monodisperse (PDI < 0.2) SCL of around 140 nm with monomodal size distributions and enhanced properties when compared to usual bulk mixing.
This article was published in the following journal.
Name: Colloids and surfaces. B, Biointerfaces
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The internal resistance of a material to moving some parts of it parallel to a fixed plane, in contrast to stretching (TENSILE STRENGTH) or compression (COMPRESSIVE STRENGTH). Ionic crystals are brittle because, when subjected to shear, ions of the same charge are brought next to each other, which causes repulsion.
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A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane.
The amount of force generated by MUSCLE CONTRACTION. Muscle strength can be measured during isometric, isotonic, or isokinetic contraction, either manually or using a device such as a MUSCLE STRENGTH DYNAMOMETER.
Therapeutic approach tailoring therapy for genetically defined subgroups of patients.
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