Electrostatics of PEGylated micelles and liposomes containing charged and neutral lipopolymers.
Abstract
The electrostatics of large unilamellar vesicles (LUVs) of various lipid compositions were determined and correlated with steric stabilization. The compositional variables studied include (a) degree of saturation, comparing the unsaturated egg phosphatidylcholine (EPC) and the fully hydrogenated soy phosphatidylcholine (HSPC) as liposome-forming lipids; (b) the effect of 40 mol % cholesterol; (c) the effect of mole % of three methyl poly(ethylene glycol) (mPEG)-lipids (the negatively charged mPEG-distearoyl phosphoethanolamine (DSPE) and two uncharged lipopolymers, mPEG-distearoyl glycerol (DSG) and mPEG-oxycarbonyl-3-amino-1,2-propanediol distearoyl ester (DS)); and (d) the negatively charged phosphatidyl glycerol (PG). The lipid phases were as follows: liquid disordered (LD) for the EPC-containing LUV, solid ordered (SO) for the HSPC-containing LUV, and liquid ordered (LO) for either of those LUV with the addition of 40 mol % cholesterol. The LUV zeta potential and electrical surface potential (psi(0)) were determined. It was found that progressive addition of mPEG(2k)-DSPE to liposomes increases negative surface potential and reduces surface pH to a similar extent as the addition of PG. However, due to the "hidden charge effect", zeta potential was more negative for liposomes containing PG than for those containing mPEG(2k)-DSPE. Replacing mPEG-DSPE with mPEG(2k)-DS or mPEG-DSG had no effect on surface pH and surface potential, and zeta potential was approximately zero. Addition of low concentrations of cationic peptides (protamine sulfate and melittin) to PG- or mPEG-DSPE-containing liposomes neutralized the liposome negative surface potential to a similar extent. However, only in liposomes containing PG, did liposome aggregation occur. Replacing the negatively charged lipopolymer mPEG-DSPE with the neutral lipopolymers mPEG-DS or mPEG-DSG eliminates or reduces such interactions. The relevance of this effect to the liposome performance in vivo is discussed.
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The final nSSL-MPS are small (mean size 83±15 nm SD) unilamellar vesicles in 5% dextrose, with a unimodal narrow size distribution and low negative charge (zeta potential of -5 mV).
“Our final nSSL-MPS are small (mean size of 83±15 nm SD) unilamellar vesicles in 5% dextrose, having a unimodal narrow size distribution and low negative charge (zeta potential of -5mV), which is related to the hindered charge of pegylated liposomes [58].”
From Fabrication Principles and Their Contribution to the Superior In Vivo Therapeutic Efficacy of Nano-Liposomes Remote Loaded with Glucocorticoids (2011) · cites this paper as [58]
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- Authors
- Garbuzenko, O., Zalipsky, S., Qazen, M., & Barenholz, Y.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Corresponding author
- Barenholz, Yechezkel
- Venue
- Langmuir
- Publisher
- American Chemical Society (ACS)
- Published
- 2005-02-10
- Volume
- 21
- Issue
- 6
- Pages
- 2560-2568
- ISSN
- 0743-7463 (ISSN-L)
- 1520-5827
- OpenAlex
- W2084413181
- Cited by
- 84
- References
- 26
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 5 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 6 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 3 · 2013: 5 · 2012: 4
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Langmuir (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Electrostatics and Colloid Interactions
- Keywords
- PEGylated liposomes, phosphatidylglycerol, zeta potential, surface potential, surface pH, cholesterol, lipid phase, liposome aggregation, cationic peptides, protamine sulfate, melittin, steric stabilization, micelles
- MeSH terms
- Hydrogen-Ion Concentration, Liposomes, Micelles, Polyethylene Glycols, Surface Properties, Static Electricity
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