Table 1.
General methods for the preparation of vesicles and the types of vesicles produced.
| Method | Description | Types of Liposomes Produced | Ref. |
|---|---|---|---|
| Physical dispersion: lipid film hydration by shaking (Bangham method) | Lipids are dissolved in a mixture of solvents in a round bottom flask; solvent evaporation leaves a thin film at the bottom that subsequently is rehydrated with an aqueous buffer. The compounds to be encapsulated can be added either at the solvent mixture or the aqueous buffer. | multilamellar and giant unilamellar vesicles Size reduction (as post-treatment): small unilamellar vesicles (micro-emulsification, bath or probe sonication followed by ultra centrifugation); oligolamellar and/or large unilamellar vesicles (membrane extrusion); small unilamellar vesicles of complex architecture (freeze-thaw sonication) |
[56] |
| Physical dispersion: lipid film hydration by non-shaking | Lipids dissolved in organic solvent are freeze dried prior to addition of aqueous buffer. Alternatively, the film is deposited on electrodes and subsequently hydrated in the presence of anelectric field. | multilamellar and giant unilamellar vesicles Size reduction: as above |
[56,57] |
| Solvent dispersion: ethanol or ether injection | Lipids in solvent are mixed with the aqueous phase that contains the components to be encapsulated. | small unilamellar vesicles | [58] |
| Solvent dispersion: reverse phase evaporation | A water-in-oil emulsion is formed; the evaporation of the organic phase produces an aqueous suspension of vesicles. | small and large unilamellar vesicles | [57] |
| Detergent solubilization: micelle–vesicle transition | Detergents are used for the solubilization of lipids in micellar systems; the vesicles are released through dilution, gel chromatography, hollow fiber dialysis, membrane filtration, or adsorption to hydrophobic matrix (resins or dextrins). | multilamellar, oligolamellar, large unilamellar vesicles (dialysis); small unilamellar vesicles (gel chromatography, filtration, adsorption) | [59] |
| Proliposomes: hydration | Proliposomes are formed by drying a lipid solution; solvent removal proceeding with rotary vacuum evaporation, fluidized bed adsorption or spray drying. When diluted in aqueous phase (along with the components to be encapsulated), a vesicle dispersion is produced; encapsulation efficiencies are high and the products can be sterilized. | multilamellar vesicles | [58] |
| Supercritical fluid technology: anti-solvent method and reverse phase evaporation | In the anti-solvent method, the lipids dissolve in supercritical CO2 and then precipitate in the form of ultra-fine particles. In reverse phase evaporation, supercritical CO2 is used instead of conventional solvents. | multilamellar and giant unilamellar vesicles (anti-solvent method); small and large unilamellar vesicles (reverse phase evaporation) | [60] |
| Microfluidic methods: hydrodynamic focusing, droplets, pulsed jet flow, thin film hydration | Microfluidics offer micro-to nanoliter volumes of vesicles dispersions and precise control over production. | small unilamellar vesicles (micro hydrodynamic focusing); giant unilamellar vesicles (microfluidic droplets and pulsed jet flow microfluidics); large unilamellar vesicles (thin film hydration in microtubes) | [57] |