Preparation of nanoliposomes by microfluidic mixing in herring-bone channel and the role of membrane fluidity in liposomes formation (original) (raw)
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Ethanol injection is widely used in liposome preparation. However, the parameters determining particle size distribution of the liposomal preparation has not been fully defined. A syringe pump-driven microfluidic injection device was used to produce liposomes under different conditions. Particle size of the liposomes was decreased with decrease in needle diameter (or increase in hydrodynamic pressure), decrease in lipid concentration in the alcohol solution, decrease in phase transition temperature (T(m)) of the lipid bilayer and the absence of cholesterol (or decrease in, membrane rigidity). The device used is simple to adopt and can be used for affordable production of liposomes with tunable particle size.
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Giant Unilamellar Vesicles (GUVs) are a versatile tool in many branches of science, including biophysics and synthetic biology. Octanol-Assisted Liposome Assembly (OLA), a recently developed microfluidic technique enables the production and testing of GUVs within a single device under highly controlled experimental conditions. It is therefore gaining significant interest as a platform for use in drug discovery, the production of artificial cells and more generally for controlled studies of the properties of lipid membranes. In this work, we expand the capabilities of the OLA technique by forming GUVs of tunable binary lipid mixtures of DOPC, DOPG and DOPE. Using fluorescence recovery after photobleaching we investigated the lateral diffusion coefficients of lipids in OLA liposomes and found the expected values in the range of 1 μm2/s for the lipid systems tested. We studied the OLA derived GUVs under a range of conditions and compared the results with electroformed vesicles. Overall...
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The aim of this work was to assess the impact of solvent selection on the microfluidic production of liposomes. To achieve this, liposomes were manufactured using small-scale and bench-scale microfluidics systems using three aqueous miscible solvents (methanol, ethanol or isopropanol, alone or in combination). Liposomes composed of different lipid compositions were manufactured using these different solvents and characterised to investigate the influence of solvents on liposome attributes. Our studies demonstrate that solvent selection is a key consideration during the microfluidics manufacturing process, not only when considering lipid solubility but also with regard to the resultant liposome critical quality attributes. In general, reducing the polarity of the solvent (from methanol to isopropanol) increased the liposome particle size without impacting liposome short-term stability or release characteristics. Furthermore, solvent combinations such as methanol/isopropanol mixtures ...
Homogeneous and reproducible liposome preparation relying on reassembly in microchannel laminar flow
Chemical Engineering Journal, 2010
We investigated a method for size homogenization of liposomes using microchannel laminar flow. This microchannel method combined with sonication produced the desired homogeneous liposome populations with size controlled by reassembly of liposomes in laminar flow, using simple operations that offer good reproducibility and organic-solvent free procedures. The liposome solution, which was prepared using the traditional method of film hydration, was loaded into a syringe. This liposome solution was sonicated while being transported into the capillary tubing using syringe injection. In both non-sonicated and sonicated batchwise preparations, liposomes displayed non-homogeneous and non-reproducible size profiles. On the other hand, homogeneous liposomes were obtained with good reproducibility using our microchannel method combined with sonication.
Please cite this article in press as: Phapal, S.M., Sunthar, P., Influence of micro-mixing on the size of liposomes self-assembled from miscible liquid phases. Chem. Phys. Lipids (2013), http://dx.a b s t r a c t Ethanol injection and variations of it are a class of methods where two miscible phases-one of which contains dissolved lipids-are mixed together leading to the self-assembly of lipid molecules to form liposomes. This method has been suggested, among other applications, for in situ synthesis of liposomes as drug delivery capsules. However, the mechanism that leads to a specific size selection of the liposomes in solution based self-assembly in general, and in flow-focussing microfluidic devices in particular, has so far not been established. Here we report two aspects of this problem. A simple and easily fabricated device for the synthesis of monodisperse unilamellar liposomes in a co-axial flow-focussing microfluidic geometry is presented. We also show that the size of liposomes is dependent on the extent of microconvective mixing of the two miscible phases. Here, a viscosity stratification induced hydrodynamic instability leads to a gentle micro-mixing which results in larger liposome size than when the streams are mixed turbulently. The results are in sharp contrast to a purely diffusive mixing in macroscopic laminar flow that was believed to occur under these conditions. Further precise quantification of the mixing characteristics should provide the insights to develop a general theory for size selection for the class of ethanol injection methods. This will also lay grounds for obtaining empirical evidence that will enable better control of liposome sizes and for designing drug encapsulation and delivery devices.
Influence of micro-mixing on the size of liposomes self-assembled from miscible liquid phases
Chemistry and Physics of Lipids, 2013
Ethanol injection and variations of it are a class of methods where two miscible phases-one of which contains dissolved lipidsare mixed together leading to the self-assembly of lipid molecules to form liposomes. This method has been suggested, among other applications, for in-situ synthesis of liposomes as drug delivery capsules. However, the mechanism that leads to a specific size selection of the liposomes in solution based self-assembly in general, and in flow-focussing microfluidic devices in particular, has so far not been established. Here we report two aspects of this problem. A simple and easily fabricated device for synthesis of monodisperse unilamellar liposomes in a co-axial flow-focussing microfluidic geometry is presented. We also show that the size of liposomes is dependent on the extent of micro-convective mixing of the two miscible phases. Here, a viscosity stratification induced hydrodynamic instability leads to a gentle micro-mixing which results in larger liposome size than when the streams are mixed turbulently. The results are in sharp contrast to a purely diffusive mixing in macroscopic laminar flow that was believed to occur under these conditions. Further precise quantification of the mixing characteristics should provide the insights to develop a general theory for size selection for the class of ethanol injection methods. This will also lay grounds for obtaining empirical evidence that will enable better control of liposome sizes and for designing drug encapsulation and delivery devices.
General Perception of Liposomes: Formation, Manufacturing and Applications
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Liposomes are currently part of the most reputed carriers for various molecular species, from small and simple to large and complex molecules. Since their discovery, liposomes have been subject to extensive evolution, in terms of composition, manufacturing and applications, which led to several openings in both basic and applied life sciences. However, most of the advances in liposome research have been more devoted to launching new developments than improving the existing technology for potential implementation. For instance, the evolution of the conventional lipid hydration methods to novel microfluidic technologies has permitted upscale production, but with increase in manufacturing cost and persistent use of organic solvents. This chapter intends to present general concepts in liposome technology, highlighting some longstanding bottlenecks that remain challenging to the preparation, characterization and applications of liposomal systems. This would enhance the understanding of the gaps in the field and, hence, provide directions for future research and developments.