Journal
LANGMUIR
Volume 35, Issue 18, Pages 6064-6074Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.langmuir.8b04256
Keywords
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Funding
- Ermenegildo Zegna Founder's Scholarship program
- Rosetrees Trust
- FP7 Marie Curie Intra-European Fellowship SMase LIPOSOME [626766]
- Swiss National Science Foundation [P300PA_171540, 406240_147493]
- i-sense Engineering and Physical Sciences Research Council (EPSRC) [1610368IRC, EP/K031953/1]
- Medical Research Council (MRC) [MR/P024378/1]
- Deutsche Forschungsgemeinschaft [KA4370/1-1]
- Wellcome Trust Senior Investigator Award [098411/Z/12/Z]
- Science and Technology Facilities Council [RB1610368, RB1710255]
- NSF [DMR-0520547]
- European Union's Horizon 2020 research and innovation programme under the SINE2020 project [654000]
- EPSRC [EP/K031953/1] Funding Source: UKRI
- MRC [MR/P024378/1] Funding Source: UKRI
- Swiss National Science Foundation (SNF) [406240_147493, P300PA_171540] Funding Source: Swiss National Science Foundation (SNF)
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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.
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