Shear-stress sensitive lenticular vesicles for targeted drug delivery

Holme, Margaret N.; Fedotenko, Illya; Abegg, Daniel; Althaus, Jasmin; Babel, Lucille; Reiter, Renate; Tanasescu, Radu; Zaffalon, Pierre Léonard; Ziegler, André; Müller, Bert; Saxer, Till; Zumbuehl, Andréas

doi:10.1038/nnano.2012.84

Cited by 258 publications

(291 citation statements)

References 47 publications

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“…Standard Pad-PC-Pad vesicles are mechanosensitive and release an entrapped fluorescent marker upon vortex shaking. 12 The softening of the membranes caused by the addition of 10 mol % cholesterol leads to a leakier membrane both under mechanical stress and at rest (Figure 9). Pad-PC-Pad vesicles containing 10 mol % cholesterol release significantly more of the entrapped dye compared to all other vesicle formulations.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Vesicle Origami and the Influence of Cholesterol on Lipid Packing

et al. 2016

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ABSTRACT:The artificial phospholipid Pad-PC-Pad was analyzed in 2D (monolayers at the air/water interface) and 3D (aqueous lipid dispersions) systems. In the gel phase, the two leaflets of a Pad-PC-Pad bilayer interdigitate completely, and the hydrophobic bilayer region has a thickness comparable to the length of a single phospholipid acyl chain. This leads to a stiff membrane with no spontaneous curvature. Forced into a vesicular structure, Pad-PC-Pad has faceted geometry, and in its extreme form, tetrahedral vesicles were found as predicted a decade ago. Above the main transition temperature, a noninterdigitated L α phase with fluid chains has been observed. The addition of cholesterol leads to a slight decrease of the main transition temperature and a gradual decrease in the transition enthalpy until the transition vanishes at 40 mol % cholesterol in the mixture. Additionally, cholesterol pulls the chains apart, and a noninterdigitated gel phase is observed. In monolayers, cholesterol has an ordering effect on liquid-expanded phases and disorders condensed phases. The wavenumbers of the methylene stretching vibration indicate the formation of a liquid-ordered phase in mixtures with 40 mol % cholesterol. ■ INTRODUCTIONVesicle origami or the guided self-assembly of a soft matter liposome may lead to materials with unprecedented properties. However, imposing a specific form on a liposome remains a formidable challenge. To achieve this goal, more fundamental insight into the forces determining the local curvature in membranes is needed.Here, we analyze the effects of membrane interdigitation and the deinterdigitating effect of cholesterol on monolayers and bilayers. Moreover, the liquid-ordered phase is characterized in unprecedented clarity.Cholesterol is a flat molecule maximizing the hydrophobic forces in model phospholipid membranes. 1 Cholesterol hereby acts as a fluidity buffer, 2 and this leveling effect leads to a liquidordered membrane phase. 3 In a nonideal mixture of low-and high-melting glycerophospholipids, cholesterol associates preferentially with the high-melting, saturated lipids. 4 Cholesterol and the glycerophospholipids interact strongly but transiently 5 via (i) hydrogen bonds between the hydroxy group of cholesterol and the phospholipid phosphodiester, 6 (ii) hydrogen bonds among the hydroxy group of cholesterol, water, and the sn-1 carbonyl moiety of the phospholipid, 7 (iii) van der Waals hydrophobic forces between the planar cholesterol ring system and the sn-1 chain of the phospholipid, 8 and, most importantly, (iv) van der Waals forces between the fatty acyl chains and the cholesterol side chain. 9 The interactions are strongly dependent on the type of phospholipid headgroup and lipid tail saturation 10 and may lead to a positioning of cholesterol in the middle of the bilayer membrane in the presence of polyunsaturated phospholipids. 11 Here, we discuss the effect of cholesterol on monolayers and bilayers formed by artificial 1,3-diamidophospholipid Pad-PCPad (structures in Figure 1). B...

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Section: ■ Results and Discussionmentioning

confidence: 99%

Vesicle Origami and the Influence of Cholesterol on Lipid Packing

et al. 2016

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“…The role of microphase separation driven by shear flow in concentrated mesophases has not been incorporated in any of the theoretical models for nonequilibrium phase transitions in bilayer-forming amphiphilic systems comprising surfactants, block copolymers, and microemulsions. Understanding shear as a strategy to control the spontaneous curvature of bilayers of mixed amphiphilic systems is also expected to have significant applications in the design of novel drug delivery systems (41), controlling the permeability of bilayers in onion phases used for encapsulation, in addition to tuning the viscosity during flow processing of surfactant-based products in consumer industry.…”

Section: Discussionmentioning

confidence: 99%

Reversible shear-induced crystallization above equilibrium freezing temperature in a lyotropic surfactant system

Rathee

Krishnaswamy

Pal

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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We demonstrate a unique shear-induced crystallization phenomenon above the equilibrium freezing temperature ðT o K Þ in weakly swollen isotropic ðL i Þ and lamellar ðL α Þ mesophases with bilayers formed in a cationic-anionic mixed surfactant system. Synchrotron rheological X-ray diffraction study reveals the crystallization transition to be reversible under shear (i.e., on stopping the shear, the nonequilibrium crystalline phase L c melts back to the equilibrium mesophase). This is different from the shear-driven crystallization below T o K , which is irreversible. Rheological optical observations show that the growth of the crystalline phase occurs through a preordering of the L i phase to an L α phase induced by shear flow, before the nucleation of the L c phase. Shear diagram of the L i phase constructed in the parameter space of shear rate ð_ γÞ vs. temperature exhibits L i → L c and L i → L α transitions above the equilibrium crystallization temperature ðT o K Þ, in addition to the irreversible shear-driven nucleation of L c in the L i phase below T o K . In addition to revealing a unique class of nonequilibrium phase transition, the present study urges a unique approach toward understanding shear-induced phenomena in concentrated mesophases of mixed amphiphilic systems.shear-induced phase separation | strongly binding counterions | coagels S hear is known to assist crystallization below the equilibrium freezing temperature in complex fluids like colloidal glasses (1, 2), dense granular suspensions (3), polymer melts (4, 5), micellar solutions of block copolymers (6), and multicomponent surfactant systems (7,8). Shear-driven crystallization is equally relevant for simple fluids like bulk metallic glasses (9), molecular liquids (10), and atomic systems (11). The general understanding is that shear lowers the energy barrier for nucleation and accelerates the growth of a stable crystalline phase from a metastable, amorphous/ isotropic solution at Peclet number Pe = σa 3 kBT > 1, where σ is the shear stress, a is the characteristic length scale, and k B T is the thermal energy (12). The crystalline phase primarily induced by the effect of flow on the internal structure and ordering of the constituents does not revert to the starting fluid state when the imposed shear is removed, indicating that the phenomenon is not a dynamic phase transition. In the present study, we report a unique phenomenon, where under steady shear, crystallization occurs above the equilibrium crystallization temperature ðT o K Þ in an isotropic mesophase ðL i Þ consisting of bilayers formed in a lyotropic surfactant system. Notably, above T o K , when the imposed shear is removed, the crystalline phase melts back to the starting L i phase.The studies were carried out in a cationic-anionic mixed surfactant system formed by SDS and the strong binding counter-ion paratoluene hydrochloride (PTHC) in water. At equilibrium, the organic counter-ion PTHC has the tendency to remain at the micelle-water interface, decreasing the spontaneous curvat...

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“…4 Even though both vesicle types are significantly larger than 40 nm, faceted vesicles were found below the main phase transition. We hypothesized that the interplay of the amido groups and the 1,3-substitution pattern would lead to a special vesicle organization with a continuous intermolecular hydrogen-bonding pattern.…”

Section: ■ Introductionmentioning

confidence: 99%

“…4 Molecules that belong to this type of phospholipids are expected to selfassemble into membranes similar to natural lipids. Nonetheless, the modified chemical structures should lead to noticeable changes in membrane biophysics.…”

Section: ■ Introductionmentioning

confidence: 99%

Monolayer Properties of 1,3-Diamidophospholipids

2013

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While nature provides an endless variety of phospholipids presenting hydrolyzable ester linkages for the 1,2-positioned hydrocarbon tails, we designed and synthesized 1,3-diamidophospholipids which contain stable fatty acid amides. These new phospholipids form faceted unilamellar vesicles with mechanosensitive properties. Aiming to understand the mechanism responsible for this behavior at a molecular level, we investigated the 1,3-diamidophospholipid family in monolayers, a simplified model membrane system. Langmuir isotherms combined with in situ grazing incidence X-ray diffraction (GIXD), specular X-ray reflectivity (XR), and infrared reflection−absorption spectroscopy (IRRAS) allowed the characterization of the monolayers from a structural and thermodynamical point of view. The existence of strong headgroup interactions due to the formation of a hydrogen-bonding network was clearly revealed by IRRAS and by the high rigidity of the monolayers. GIXD showed that only the longer chain compounds of the series (Pad-PC-Pad (1,3-dipalmitamidopropan-2-phosphocholine) and Sad-PC-Sad (1,3-distearamidopropan-2-phosphocholine) were able to form ordered monolayers. The chains are strongly tilted in a rigid lattice formed due to these hydrogenbonding interactions between the headgroups. The thermodynamical analysis leads to a critical temperature of the monolayer which is clearly different from the main phase transition temperature in bulk, indicating that there must be a different structural arrangement of the 1,3-diamidophospholipids in monolayers and in bilayers.

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Shear-stress sensitive lenticular vesicles for targeted drug delivery

Cited by 258 publications

References 47 publications

Vesicle Origami and the Influence of Cholesterol on Lipid Packing

Vesicle Origami and the Influence of Cholesterol on Lipid Packing

Reversible shear-induced crystallization above equilibrium freezing temperature in a lyotropic surfactant system

Monolayer Properties of 1,3-Diamidophospholipids

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