Properties of Liposomes Containing Natural and Synthetic Lipids Formed by Microfluidic Mixing (original) (raw)
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A facile microfluidic method for production of liposomes
Anticancer research
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.
2019
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...
General Perception of Liposomes: Formation, Manufacturing and Applications
Liposomes - Advances and Perspectives [Working Title]
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.
Scientific Reports, 2020
Introduction of microfluidic mixing technique opens a new door for preparation of the liposomes and lipid-based nanoparticles by on-chip technologies that are applicable in a laboratory and industrial scale. This study demonstrates the role of phospholipid bilayer fragment as the key intermediate in the mechanism of liposome formation by microfluidic mixing in the channel with "herring-bone" geometry used with the instrument NanoAssemblr. The fluidity of the lipid bilayer expressed as fluorescence anisotropy of the probe N,N,N-Trimethyl-4-(6-phenyl-1,3,5-hexatrien-1-yl) was found to be the basic parameter affecting the final size of formed liposomes prepared by microfluidic mixing of an ethanol solution of lipids and water phase. Both saturated and unsaturated lipids together with various content of cholesterol were used for liposome preparation and it was demonstrated, that an increase in fluidity results in a decrease of liposome size as analyzed by DLS. Gadolinium chelating lipids were used to visualize the fine structure of liposomes and bilayer fragments by CryoTEM. Experimental data and theoretical calculations are in good accordance with the theory of lipid disc micelle vesiculation.
Pharmaceutics, 2019
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 ...
Evaluation of a static mixer as a new microfluidic method for liposome formulation
Frontiers in Bioengineering and Biotechnology, 2023
Introduction: Microfluidic formulation of liposomes has been extensively studied as a potential replacement for batch methods, which struggle with problems in scalability and difficulty in modulating conditions. Although microfluidic devices are considered to be able to combat these issues, an adequate replacement method has yet to be established. Methods: This paper examines the potential of a static mixer (SM) by comparing the encapsulation efficiency, loading, lamellarity, and user-friendliness with a commonly used microfluidic device, a staggered herringbone micromixer (SHM). Results: In both devices, it was found that as the initial lipid concentration increased, the particle size increased; however, the overall particle size was seen to be significantly larger in the liposomes prepared with SM. PDI remained significantly smaller in SM, however, signifying that better control of the particle size was accomplished in SM. In addition, the encapsulation efficiency was slightly smaller in SM compared to SHM, and in both devices, the values increased as the initial lipid concentration increased. The increase in encapsulation efficiencies was significantly smaller than that of the theoretical encapsulation efficiency, and this was found to be due to the increase in lamellarity as the initial lipid concentration increased. Discussion: In terms of user-friendliness, SM demonstrated significant advantages. The mixing elements could be taken out from the device, allowing for thorough cleaning of the element and device before and after experiments and ensuring experiments are conducted at virgin state in every round. Consequently, it was found that SM not only can produce uniformly distributed liposomes but has the potential to become a more practical method for liposome formulation with modifications in the mixing elements.
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.
Advances in Liposomes Research
In this book the authors present current research in the study of liposomes. Topics discusses in this compilation include liposome mediated malaria vaccine development; liposomal delivery of antimicrobial agents in advances in liposome research; trends on microfluidic liposome production through hydrodynamic flow-focusing and microdroplet techniques for gene delivery applications; liposomes as important drug carriers in cancer therapy; liposome application in the veterinary field; and design of liposomes with a pH-sensitive fluorescent dye and gramicidin channels for immune-sensing. (Imprint: Nova)
Preparation of Liposomes from Milk Fat Globule Membrane Phospholipids Using a Microfluidizer
Journal of Dairy Science, 2006
The isolation of milk fat globule membrane (MFGM) material from buttermilk on a commercial scale has provided a new ingredient rich in phospholipids and sphingolipids. An MFGM-derived phospholipid fraction was used to produce liposomes via a high-pressure homogenizer (Microfluidizer). This technique does not require the use of solvents or detergents, and is suitable for use in the food industry. The liposome dispersion had an average hydrodynamic diameter of 95 nm, with a broad particle-size distribution. Increasing the number of passes through the Microfluidizer, increasing the pressure, or reducing the phospholipid concentration all resulted in a smaller average liposome diameter. Changing these variables did not have a significant effect on the polydispersity of the dispersion. Electron microscopy showed that the dispersions formed had a range of structures, including unilamellar, multilamellar, and multivesicular liposomes. The composition of the MFGM phospholipid material is different from that of the phospholipids usually used for liposome production in the pharmaceutical and cosmetic industries. The MFGM-derived fraction comprises approximately 25% sphingomyelin, and the fatty acids are primarily saturated and monounsaturated. These differences are likely to affect the properties of the liposomes produced from the phospholipid material, and it may be possible to exploit the unique composition of the MFGM phospholipid fraction in the delivery of bioactive ingredients in functional foods.