Insertion stability of poly(ethylene glycol)-cholesteryl-based lipid anchors in liposome membranes

Molnar, Daniel; Linders, Jürgen; Mayer, Christian; Schubert, Rolf

doi:10.1016/j.ejpb.2016.03.023

Cited by 17 publications

(12 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pegylation of liposomes with compatible length of PEG has been a known procedure to improve the liposome stability in vivo, especially in blood circulation [25]. Studies have also consistently showed that long PEG chains positively correlate with significantly more release from the liposome membranes [26]. On the other hand, fluorescent lipophilic membrane dyes (e.g., long-chain dicarbocyanine) are widely used to label plasma membrane for long-term cell tracking in vivo.…”

Section: Resultsmentioning

confidence: 99%

Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes

et al. 2021

Membranes

View full text Add to dashboard Cite

Cell-based therapies have the potential to transform the treatment of many diseases. One of the key challenges relating to cell therapies is to modify the cell surface with molecules to modulate cell functions such as targeting, adhesion, migration, and cell–cell interactions, or to deliver drug cargos. Noncovalent insertion of lipid-based amphiphilic molecules on the cell surface is a rapid and nontoxic approach for modifying cells with a variety of bioactive molecules without affecting the cellular functions and viability. A wide variety of lipid amphiphiles, including proteins/peptides, carbohydrates, oligonucleotides, drugs, and synthetic polymers have been designed to spontaneously anchor on the plasma membranes. These molecules typically contain a functional component, a spacer, and a long chain diacyl lipid. Though these molecular constructs appeared to be stably tethered on cell surfaces both in vitro and in vivo under static situations, their stability under mechanical stress (e.g., in the blood flow) remains unclear. Using diacyl lipid-polyethylene glycol (lipo-PEG) conjugates as model amphiphiles, here we report the effect of molecular structures on the amphiphile stability on cell surface under mechanical stress. We analyzed the retention kinetics of lipo-PEGs on erythrocytes in vitro and in vivo and found that under mechanical stress, both the molecular structures of lipid and the PEG spacer have a profound effect on the membrane retention of membrane-anchored amphiphiles. Our findings highlight the importance of molecular design on the dynamic stability of membrane-anchored amphiphiles.

show abstract

Section: Resultsmentioning

confidence: 99%

Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes

et al. 2021

Membranes

View full text Add to dashboard Cite

show abstract

“…Due to the higher phase-transition temperature of phospholipids, a higher activation energy is needed for their successful insertion, while cholesterol inserts more easily. This is reflected in a lower incubation-temperature of as low as 17 °C being needed for cholesterol-insertion as opposed to the insertion of phospholipids that is typically performed at 60 °C [102]. A disadvantage of both variants is the possibility of transferring the inserted molecules in vivo to other available membranes and serum proteins [102,103].…”

Section: Lipid-post-insertion Into the Ev-membranementioning

confidence: 99%

“…This is reflected in a lower incubation-temperature of as low as 17 °C being needed for cholesterol-insertion as opposed to the insertion of phospholipids that is typically performed at 60 °C [102]. A disadvantage of both variants is the possibility of transferring the inserted molecules in vivo to other available membranes and serum proteins [102,103]. While the temperature-requirements for cholesterol-post-insertion are more suitable for application in EVs, the lower insertion stability of cholesterol-anchored molecules is a disadvantage to be considered.…”

Section: Lipid-post-insertion Into the Ev-membranementioning

confidence: 99%

“…While surface-modification of EVs by insertion of lipophilic moieties has been realized in different applications, the question of insertion stability under in vivo conditions warrants special evaluation, as liposomes treated with cholesterol-post-insertion demonstrates only a low retention of inserted lipids [102]. Without sufficient insertion stability, the applicability of membrane insertion for drug delivery and EV-targeting would be very limited.…”

Section: Lipid-post-insertion Into the Ev-membranementioning

confidence: 99%

See 1 more Smart Citation

Approaches to surface engineering of extracellular vesicles

Richter

Vader

Fuhrmann

2021

Advanced Drug Delivery Reviews

124

View full text Add to dashboard Cite

“…Of particular note, liposomes have low stability in their aqueous dosage form. This is the main issue that limits liposomal shelf-life, which can be caused by the fusion of liposomes or leakage of encapsulated substances after long-term storage [9,10,11]. Other processes to solidify liposomes, such as freeze drying or spray drying, also introduced stress-induced instability into the liposomal system [12].…”

Section: Introductionmentioning

confidence: 99%

Optimization of Polyarginine-Conjugated PEG Lipid Grafted Proliposome Formulation for Enhanced Cellular Association of a Protein Drug

et al. 2019

View full text Add to dashboard Cite

The purpose of this study was to develop an oral proliposomal powder of protein using poly-l-arginine-conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) (PLD) for enhancing cellular association upon reconstitution and to compare its effects with a non-grafted and PEGylated formulation. Cationic proliposome (CATL), PLD-grafted CATL (PLD-CATL), PEGylated CATL (PEG CATL), and PLD grafted-PEG CATL (PLD-PEG CATL) were prepared and compared. Successful conjugation between poly-l-arginine and DSPE-PEG was confirmed by 1H NMR and FT-IR. PLD was successfully grafted onto the proliposomal powder during the slurry process. Although reconstituted liposomal sizes of CATL and PLD-CATL were increased by agglomeration, PEGylation reduced the agglomeration and increased the encapsulation. The viabilities of cells treated with both CATL and PLD-CATL formulations were low but increased following PEGylation. With regard to cellular association, PLD-CATL enhanced cellular association/uptake more rapidly than did CATL. Upon PEGylation, PEG CATL showed a lower level of cellular association/uptake compared with CATL while PLD-PEG CATL did not exhibit the rapid cellular association/uptake as seen with PLD-CATL. However, PLD-PEG CATL still enhanced the higher cellular association/uptake than PEG CATL did without PLD. In conclusion, proliposomes with PLD could accelerate cellular association/uptake but also caused high cellular toxicity. PEGylation reduced cellular toxicity and also changed the cellular association pattern of the PLD formulation.

show abstract

Insertion stability of poly(ethylene glycol)-cholesteryl-based lipid anchors in liposome membranes

Cited by 17 publications

References 58 publications

Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes

Structure-Dependent Stability of Lipid-Based Polymer Amphiphiles Inserted on Erythrocytes

Approaches to surface engineering of extracellular vesicles

Optimization of Polyarginine-Conjugated PEG Lipid Grafted Proliposome Formulation for Enhanced Cellular Association of a Protein Drug

Contact Info

Product

Resources

About