Effect of Formulation Method, Lipid Composition, and PEGylation on Vesicle Lamellarity : A Small-Angle Neutron Scattering Study

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 encapsula...

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Veröffentlicht in:Langmuir : the ACS journal of surfaces and colloids. - 1992. - 35(2019), 18 vom: 07. Mai, Seite 6064-6074
1. Verfasser: Nele, Valeria (VerfasserIn)
Weitere Verfasser: Holme, Margaret N, Kauscher, Ulrike, Thomas, Michael R, Doutch, James J, Stevens, Molly M
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2019
Zugriff auf das übergeordnete Werk:Langmuir : the ACS journal of surfaces and colloids
Schlagworte:Journal Article Research Support, Non-U.S. Gov't
Beschreibung
Zusammenfassung: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
Beschreibung:Date Completed 25.06.2020
Date Revised 29.01.2022
published: Print-Electronic
Citation Status PubMed-not-MEDLINE
ISSN:1520-5827
DOI:10.1021/acs.langmuir.8b04256