eprintid: 10093888
rev_number: 14
eprint_status: archive
userid: 608
dir: disk0/10/09/38/88
datestamp: 2020-03-24 17:25:11
lastmod: 2021-09-22 22:09:36
status_changed: 2020-03-24 17:25:11
type: article
metadata_visibility: show
creators_name: Nele, V
creators_name: Holme, MN
creators_name: Kauscher, U
creators_name: Thomas, MR
creators_name: Doutch, JJ
creators_name: Stevens, MM
title: Effect of Formulation Method, Lipid Composition, and PEGylation on Vesicle Lamellarity: A Small-Angle Neutron Scattering Study
ispublished: pub
divisions: UCL
divisions: B04
divisions: C06
divisions: F64
keywords: Vesicles, Lipids, Membranes, Chemical structure, Extrusion
note: This is an open access article published under a Creative Commons Attribution (CC-BY)
License, which permits unrestricted use, distribution and reproduction in any medium,
provided the author and source are cited.
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.
date: 2019-05-07
date_type: published
publisher: AMER CHEMICAL SOC
official_url: https://doi.org/10.1021/acs.langmuir.8b04256
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1726401
doi: 10.1021/acs.langmuir.8b04256
lyricists_name: Thomas, Michael
lyricists_id: MTHOA12
actors_name: Thomas, Michael
actors_id: MTHOA12
actors_role: owner
full_text_status: public
publication: Langmuir
volume: 35
number: 18
pagerange: 6064-6074
pages: 11
citation:        Nele, V;    Holme, MN;    Kauscher, U;    Thomas, MR;    Doutch, JJ;    Stevens, MM;      (2019)    Effect of Formulation Method, Lipid Composition, and PEGylation on Vesicle Lamellarity: A Small-Angle Neutron Scattering Study.                   Langmuir , 35  (18)   pp. 6064-6074.    10.1021/acs.langmuir.8b04256 <https://doi.org/10.1021/acs.langmuir.8b04256>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10093888/1/Effect%20of%20Formulation%20Method%2C%20Lipid%20Composition%2C%20and%20PEGylation%20on%20Vesicle%20Lamellarity%20A%20Small-Angle%20Neutron%20Scattering%20Stud.pdf