Poly(ethylene glycol)-induced and temperature-dependent phase separation in fluid binary phospholipid membranes

Lehtonen, Jukka; Kinnunen, Paavo K.J.

doi:10.1016/s0006-3495(95)80214-6

Cited by 85 publications

(74 citation statements)

References 134 publications

(135 reference statements)

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“…If we consider two negatively charged membranes embedded in a polyelectrolyte solution, ions tend to accumulate into the interlamellar space to shield the electrostatic repulsion between membranes, promoting the exclusion of polymer (salting-out mechanism). As a consequence of the electro-osmotic release of polymer, negatively charged membranes feel each other at longer distances than neutral membranes, as hypothesized by some authors on the basis of experimental evidence 29,30 and proved by us by electrostatic modelling and MD simulations. 8 33,34 Calcium ions trigger this event by constricting the lipid headgroups in a partially dehydrated state.…”

Section: Discussionmentioning

confidence: 63%

Simulation of polyethylene glycol and calcium-mediated membrane fusion

Pannuzzo

Jong

Raudino

et al. 2014

The Journal of Chemical Physics

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Anomalous viscosity effect in the early stages of the ion-assisted adhesion/fusion event between lipid bilayers: A theoretical and computational study J. Chem. Phys. 138, 234901 (2013) We report on the mechanism of membrane fusion mediated by polyethylene glycol (PEG) and Ca 2+ by means of a coarse-grained molecular dynamics simulation approach. Our data provide a detailed view on the role of cations and polymer in modulating the interaction between negatively charged apposed membranes. The PEG chains cause a reduction of the inter-lamellar distance and cause an increase in concentration of divalent cations. When thermally driven fluctuations bring the membranes at close contact, a switch from cis to trans Ca 2+ -lipid complexes stabilizes a focal contact acting as a nucleation site for further expansion of the adhesion region. Flipping of lipid tails induces subsequent stalk formation. Together, our results provide a molecular explanation for the synergistic effect of Ca 2+ and PEG on membrane fusion. © 2014 AIP Publishing LLC.

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Section: Discussionmentioning

confidence: 63%

Simulation of polyethylene glycol and calcium-mediated membrane fusion

Pannuzzo

Jong

Raudino

et al. 2014

The Journal of Chemical Physics

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“…[23][24][25][26] It contributes substantially to the understanding of interactions between Fe 3 O 4 @MEO 2 MA 90 -co-OEGMA 10 NPs and DPPC molecules in 2D model membranes.…”

Section: Discussionmentioning

confidence: 99%

Polymer-capped magnetite nanoparticles change the 2D structure of DPPC model membranes

2012

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The interaction of biocompatible and stimuli-responsive Fe 3 O 4 nanoparticles (NPs) with DPPC model membranes was studied at the air-water interface. The pure NPs, pure DPPC and mixed DPPC-NP Langmuir layers have been characterized in situ by compression-expansion isotherms, infrared reflection-absorption spectrometry (IRRAS), grazing incidence X-ray diffraction (GIXD), total reflection X-ray fluorescence (TRXF), Brewster angle microscopy, and by atomic force microscopy after transfer onto a solid support. When dispersed in aqueous solution, the NPs are able to penetrate the phospholipid monolayer and to occupy a certain part of the interface defined by their own surface activity. The study reveals a largely phase separated system which actually masks an important interplay between the two compounds. Detailed GIXD measurements prove that the NPs are able to change the DPPC monolayer structure in a highly cooperative way by inducing a tighter in-plane packing. As IRRAS additionally supports, the effective size of the phospholipid polar head group is reduced due to partial dehydration and reorientation. The most surprising observation is the rigidification of the DPPC-NPs composite in a large range of surface pressures. Above the critical pressure, the phase separated NPs are squeezed out but the ones interacting with the DPPC molecules stay in the layer up to much higher lateral pressures. The interactions between NPs and DPPC stabilize the NPs at the interface. Only at very high pressures, all NPs are squeezed out. The amount of NPs in the monolayer has been quantified by TRXF. The desorption process is kinetically hindered.

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“…[17][18][19] Liposomal PTX formulations that are currently on the market (Lipusu ) all use unsaturated PC (1,2-dioleoyl-snglycero-3-phosphocholine or EggPC) without PEGylated lipid supplementation, probably owing to these limitations in the stability of PTX-loaded liposomes. [20][21][22] Saturated PCs, however, tend to produce liposomes that retain loaded drugs longer than unsaturated PCs, owing to the absence of oxidation-prone bonds and the higher phase-transition temperature of the resulting liposomes [23][24][25] and PEGylation of liposomes extends the circulation time of loaded drugs in the bloodstream and thus increase drug accumulation in tumors 26 by reducing interactions of liposomes with the reticuloendothelial system. Therefore, a formulation stabilizer enabling the PEGylated/saturated PC-based liposomes to retain PTX stably may provide an injectable PTX formulation with improved clinical performance.…”

Section: Introductionmentioning

confidence: 99%

Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation

Hong

Choi

Kim

et al. 2016

IJN

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Studies have highlighted the challenge of developing injectable liposomes as a paclitaxel (PTX) carrier, a challenge attributable to the limitations in liposomal stability caused by PTX loading. Poor stability of PTX-loaded liposomes is caused by PTX-triggered aggregation or fusion of liposomal membranes and is exacerbated in the presence of PEGylated lipid. In the present study, the effect of triglyceride incorporation on the stability of PTX-loaded/PEGylated liposomes was explored. Incorporation of a medium chain triglyceride Captex 300 into saturated phosphatidylcholine (PC)-based liposomes (1,2-dimyristoyl- sn -glycero-3-phosphocholine [DMPC]:cholesterol [CHOL]:N-(Carbonyl-methoxypolyethyleneglycol 2000)-1, 2-distearoyl- sn -glycero-3-phospho-ethanolamine [PE-PEG]), produced a fine, homogeneous, and membrane-filterable PTX-loaded liposomes fulfilling the requirement of an injectable lipid formulation. Triglyceride incorporation also greatly inhibited the time-dependent leakage of PTX from saturated PC-based liposomes, which appears to be mediated by the inhibition of liposome fusion. In contrast, triglyceride incorporation induced the destabilization and PTX leakage of unsaturated PC-based liposomes, indicating the opposite effect of triglyceride depending on the fluidity status of PC constituting the liposomal membrane. PTX release profile and the in vitro and in vivo anticancer efficacy of triglyceride-incorporated DMPC:CHOL:PE-PEG liposomes were similar to Taxol ® while the toxicity of liposomal PTX was significantly lower than that of Taxol. Taken together, triglyceride incorporation provided an injectable PTX formulation by functioning as a formulation stabilizer of PEGylated/saturated PC-based liposomes.

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Poly(ethylene glycol)-induced and temperature-dependent phase separation in fluid binary phospholipid membranes

Cited by 85 publications

References 134 publications

Simulation of polyethylene glycol and calcium-mediated membrane fusion

Simulation of polyethylene glycol and calcium-mediated membrane fusion

Polymer-capped magnetite nanoparticles change the 2D structure of DPPC model membranes

Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation

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