Effect of Formulation Method, Lipid Composition, and PEGylation on Vesicle Lamellarity: A Small-Angle Neutron Scattering Study
Year: 2019
Type: article
Abstract: Liposomes are well-established systems for drug delivery and biosensing applications. The design of a liposomal carrier requires careful choice of lipid composition and formulation method. These determine many vesicle properties including lamellarity, which can have a strong effect on both encapsulation efficiency and the efflux rate of encapsulated active compounds. Despite this, a comprehensive study on how the lipid composition and formulation method affect vesicle lamellarity is still lacking. Here, we combine small-angle neutron scattering and cryogenic transmission electron microscopy to study the effect of three different well-established formulation methods followed by extrusion through 100 nm polycarbonate membranes on the resulting vesicle membrane structure. Specifically, we examine vesicles formulated from the commonly used phospholipids 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphocholine (POPC), 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl- sn-glycero-3-phosphocholine (DOPC) via film hydration followed by (i) agitation on a shaker or (ii) freeze-thawing, or (iii) the reverse-phase evaporation vesicle method. After extrusion, up to half of the total lipid content is still assembled into multilamellar structures. However, we achieved unilamellar vesicle populations when as little as 0.1 mol % PEG-modified lipid was included in the vesicle formulation. Interestingly, DPPC with 5 mol % PEGylated lipid produces a combination of cylindrical micelles and vesicles. In conclusion, our results provide important insights into the effect of the formulation method and lipid composition on producing liposomes with a defined membrane structure.
Source: Langmuir
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $5,000
Awards: Hybrid Vesicles for Cardiovascular Therapeutics, G2861664341, G4236464703, NRP 62 PhD Award: Liposome/Gold nanoparticle phospholipase assay for specific detection of PLD and PLC in the presence of PLA1 and PLA2, G5170841131, World class Science and Innovation with Neutrons in Europe 2020 – SINE2020, Exploring and Engineering the Cell-Material Interface for Regenerative Medicine., m-Africa: Building mobile phone-connected diagnostics and online care pathways to support HIV prevention and management in decentralised settings., G8011031682, EPSRC IRC in Early-Warning Sensing Systems for Infectious Diseases
OpenAlex ID: W2940165911