Monitoring the Formation of Small Unilamellar Liposomes Generated by the Detergent Removal Method

Small unilamellar liposomes/vesicles (SUVs) are spherical structures < 100 nm bound by a single lipid bilayer, which are used as carriers for targeted drug delivery. The detergent-removal method of SUV preparation consists in generating a mixture between amphiphilic lipids and a detergent, then removing the latter by dialysis. By monitoring both the size and the zeta potential of particles using a Litesizer™, we determined the optimal ratio between phospholipids and either taurocholic acid or sodium cholate detergents for SUV generation.

Liposomes are spherical vesicles most often composed of phospholipids. The phospholipids are amphiphilic molecules, with a hydrophilic head group and a hydrophobic tail. By hydration, and in order to reduce thermodynamically unfavorable interactions with the aqueous medium, the hydrophobic chains form lipid bilayers (lamellae). These can then reorganize into liposomes, which are spherical structures with a central aqueous compartment.

Thanks to their special structure, liposomes can be used as drug delivery vehicles for both hydrophilic compounds, which can be dissolved into the aqueous core, and hydrophobic (lipophilic) compounds, which may be entrapped into the lipid bilayers. Specific interest for Small Unilamellar Vesicles (SUVs), a sub-class of liposomes defined by their diameter of less than 100 nm, has recently increased due to their comparably long lifetime in human plasma and their site-specific drug release potential, most notably in tumor tissues. 

In the present application report, we investigated SUVs prepared using the detergent-removal method. Using the Litesizer™ 500 particle analyzer, we have compared the size and zeta potential of SUVs generated with different anionic detergents and using varying lipid/detergent molar ratios. Furthermore, the dynamics of SUV formation during the detergent-removal process could be investigated by performing measurements before and after the different dialysis steps.

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