Formation mechanism of self-assembled unilamellar vesiclesSpecial issue on Neutron Scattering in Canada

Nieh, Mu‐Ping; Kučerka, Norbert; Katsaras, John

doi:10.1139/p10-014

Cited by 8 publications

(4 citation statements)

References 32 publications

(48 reference statements)

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“…The thermoresponsiveness of these samples is in well agreement with our results presented in Figure . The probable closure of sheets to SUVs or reorganization of micelles to vesicles was extensively discussed by other authors for different systems and varying conditions, such as heating and cooling. − The vesicle formation may be enhanced by ibuprofen and is not observed for aescin because of the reduced interactions to neighboring sheets or vesicles. However, this hypothesis is based on a single experimental indication, and this question will be addressed in detail in a future study when evaluating also the effect of higher amounts of aescin at similar drug content.…”

Section: Resultsmentioning

confidence: 99%

Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes

et al. 2018

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In the present work, we study the interaction of the saponin aescin with the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen at concentrations of 1.2-2.5 mM. These amounts are higher than those usually used for medication (10-300 μM) to show possible structures and formulations for orally absorbed drug delivery systems. It is shown how the interaction of both substances, separately or together, alters the thermotropic phase behavior of the 1,2-dimyristoyl- sn-glycero-3-phosphocholine (DMPC) bilayer in the presence of different amounts of aescin, ranging from 20 μM to 1 mM. The methods of choice are differential scanning calorimetry (DSC), and additionally wide-angle (WAXS) and small-angle X-ray scattering (SAXS). We found that these two additives, aescin and ibuprofen, alter the temperature-dependent structural appearance of the DMPC membrane depending on the aescin and drug content. The presence of the saponin and the drug become visible on different length scales, i.e., ranging from a global structural change to inner-membrane interactions. DSC reveals that the drug and saponin alter the cooperativity of the DMPC phase transition in a concentration-dependent manner. Furthermore, there is a significant difference between the drug-containing compared to the drug-free systems. By WAXS, we could resolve that aescin reverses the strong impact of ibuprofen on the diffraction peak of DMPC. Both molecules interact strongly with the phospholipid headgroups. This becomes visible in a changing area per lipid and shifting phase transition to higher temperatures. SAXS experiments reveal that the addition of ibuprofen leads to major morphological changes in the phospholipid bilayer. SAXS experiments performed on representative samples do not only cover the drug-saponin interaction within the bilayer from the structural perspective but also confirm the visually observed macroscopic concentration and temperature-dependent phase behavior. Vesicular shape of extruded samples is conserved at low aescin contents. At intermediate aescin content, aggregation between vesicles occurs, whereby the strength of aggregation is reduced by ibuprofen. At high aescin contents, DMPC bilayers are solubilized. The kind of formed structures depends on temperature and drug content. At low temperature, separated bilayer sheets are formed. Their size increases with ibuprofen in a concentration-dependent manner. At high temperature, the drug-free system reorganizes into stacked sheets. Whereas sheets at 5 mol % ibuprofen close to vesicles, the ones with 10 mol % of the drug increase massively in size. Altogether, ibuprofen was found to rather enhance than inhibit structural and thermotropic membrane modifications induced by the aescin on the DMPC model membrane.

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Section: Resultsmentioning

confidence: 99%

Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes

et al. 2018

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“…An increase in slope in the low q zone and shift of the plot to lower q region are manifestations of the formation of a large bilayered structure. 98,100 Analysis of the data by the SASFIT program 101 shows that the observed change in the SANS plot with increase in temperature is indeed associated with a change in the structure of the aggregates present in the solution. The plot at 30 °C can be fit based on a rod-like structure having 4.1 nm radius and 14.6 nm length.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Solubilization of Parabens in Aqueous Pluronic Solutions: Investigating the Micellar Growth and Interaction as a Function of Paraben Composition

Khimani

Ganguly

Aswal³

et al. 2012

J. Phys. Chem. B

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The influence of methyl paraben (MP) and butyl paraben (BP) on the aggregation characteristics of Pluronics in an aqueous medium has been investigated by DLS, SANS, viscometry, and fluorescence measurement techniques. Parabens are extensively used as preservatives in cosmetic, pharmaceutical, and food products. In this paper, we show that their influence on the restructuring and growth of Pluronics micelles vary quite significantly with their aqueous solubility and with the composition of Pluronics. In the case of P105 and P104, MP reduces the sphere-to-rod transition temperature down to room temperature, but BP with significantly less aqueous solubility than MP suppresses such micellar transition and leads to the formation of micellar clusters due to the onset of intermicellar attractive interaction. In the case of more hydrophobic Pluronic P103, on the other hand, both MP and BP are able to induce rapid room temperature sphere-to-rod micellar growth, which is not observed in the presence of water structure making salts like NaCl and Na(3)PO(4). These observations have been attributed to modulation of growth and restructuring processes of the Pluronic micelles arising due to different locations of parabens within the micellar corona as determined by their aqueous solubility and the hydrophobicity of the Pluronics.

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“…Uniform size self-assembled unilamellar vesicles (ULVs) can be produced from mixtures of weakly charged short- and long-chain phospholipids. In [ 62 , 63 ] the effect of various parameters—lipid concentration and composition, charge density and membrane rigidity on ULVs—was systematically investigated by SANS. Below the Krafft temperature, nanodisk-like aggregates are favored where the shorter chains form the rim of the disk.…”

Section: Sans For the Characterization Of Liposome Nanocarriersmentioning

confidence: 99%

Small Angle X-ray and Neutron Scattering: Powerful Tools for Studying the Structure of Drug-Loaded Liposomes

2016

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Nanovectors, such as liposomes, micelles and lipid nanoparticles, are recognized as efficient platforms for delivering therapeutic agents, especially those with low solubility in water. Besides being safe and non-toxic, drug carriers with improved performance should meet the requirements of (i) appropriate size and shape and (ii) cargo upload/release with unmodified properties. Structural issues are of primary importance to control the mechanism of action of loaded vectors. Overall properties, such as mean diameter and surface charge, can be obtained using bench instruments (Dynamic Light Scattering and Zeta potential). However, techniques with higher space and time resolution are needed for in-depth structural characterization. Small-angle X-ray (SAXS) and neutron (SANS) scattering techniques provide information at the nanoscale and have therefore been largely used to investigate nanovectors loaded with drugs or other biologically relevant molecules. Here we revise recent applications of these complementary scattering techniques in the field of drug delivery in pharmaceutics and medicine with a focus to liposomal carriers. In particular, we highlight those aspects that can be more commonly accessed by the interested users.

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Formation mechanism of self-assembled unilamellar vesiclesSpecial issue on Neutron Scattering in Canada

Cited by 8 publications

References 32 publications

Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes

Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes

Solubilization of Parabens in Aqueous Pluronic Solutions: Investigating the Micellar Growth and Interaction as a Function of Paraben Composition

Small Angle X-ray and Neutron Scattering: Powerful Tools for Studying the Structure of Drug-Loaded Liposomes

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