Vesicles stability

The interest in vesicles as models for cell biomembranes has led to much work on the interactions within and between lipid layers. The primary contributions to vesicle stability and curvature include those familiar to us already, the electrostatic interactions between charged head groups (Chapter V) and the van der Waals interaction between layers (Chapter VI). An additional force due to thermal fluctuations in membranes produces a steric repulsion between membranes known as the Helfrich or undulation interaction. This force has been quantified by Sackmann and co-workers using reflection interference contrast microscopy to monitor vesicles weakly adhering to a solid substrate [78]. Membrane fluctuation forces may influence the interactions between proteins embedded in them [79]. Finally, in balance with these forces, bending elasticity helps determine shape transitions [80], interactions between inclusions [81], aggregation of membrane junctions [82], and unbinding of pinched membranes [83]. Specific interactions between membrane embedded receptors add an additional complication to biomembrane behavior. These have been stud-... 

Strauss G, Schurtenberger P, Hauser H. The interaction of saccharides with lipid bilayer vesicles stabilization during freeze-thawing and freeze-drying. Bio-chim Biophys Acta 1986 858 169. 

Supporting the bilayer surfaces by synthetic polymer scaffolds (Figure 4.6) enables one to enhance the vesicle stability and to control the permeability of their membranes. The polymers can be embedded within the vesicles among... 

In an attempt to overcome the problem of accumulation of the oxidized electron donor, we have incorporated a recyclable surface-active electron donor in DODAC vesicles (12). This electron donor contains a sulfide moiety which dimerizes upon light-induced oxidation. Simultaneously, hydrogen is evolved via vesicle-stabilized, catalyst-coated, colloidal CdS particles. The dimer could be chemically reduced for additional hydrogen formation. Figure 9 is an idealized view of this cyclic process (12). 

Fig. 3 Vesicle stabilization by PLL covering (a, b), followed by separation of well-covered single vesicles from excess of nonbound PLL (b, c). Native vesicles are ruptured upon adsorption on a (PLL/HA)i2/PLL film, forming a lipidic bilayer (a, d). Free non-bound PLL is preferably adsorbed on a (PLL/HA)i2 film rather than on PLL-covered vesicles (b, e). Liposome-containing film (PLL/HA)i2/Lip-PLL/HA/PLL/HAis formed by adsorption of PLL-covered liposomes (Lip-PLL) on a (PLL/HA)i2 film, followed by additional coating with HA/PLL/HA layers (c, f). Reproduced from [82]...

The fact that no apparent fusion of the vesicles is revealed by the atomic force microscopy (AFM) does not prove the liposome structural integrity (Fig. 4c, d). Analysis of the profiles of the embedded vesicles show that they are immersed in the film, suggesting the immersion by two different modes of the capping film layers (1) exponential between the vesicles, and (2) linear on the vesicle top [82], Evidence of vesicle stability is proved by a direct release study of the vesicle-encapsulated CF marker, as shown in Fig. 4f [82]. Similar results were found for DPPC vesicles filled with ferrocyanide ions [77], No considerable release of the markers, at least during the first few hours after embedding, points to vesicle integrity. 

Components of a photosystem can be inserted selectively into the lipid wall or the inner cavity of the vesicle. For this purpose the lipid and components insoluble in water are dispersed together in aqueous solution by sonification. This leads to an occlusion of water insoluble components within the lipid bilayer. The vesicle membrane is sufficiently stable and impermeable for a number of ions. This allows one to prepare, by gel-filtering, the media of different ionic composition inside and outside the vesicle as shown in Fig. 2b. Such asymmetry of chemical content can be preserved for a rather long time (from several hours to several days). Recently the surfactant molecules with double bonds, which can be polymerized after vesicle preparation, were used for further enhancement of vesicle stability [37-39]. Such polymerized vesicles are stable for several months. 

The best vesicle stabilization effect was obtained by polymerization of buta-diyne units within the hydrocarbon chains of amphiphiles after the vesicle was formed. This polymerization produces red or blue polyenes and occurs only if the vesicle membrane is in the liquid crystalline state. No polymers formed... 

Fig. 19 Cyclodextrin vesicles stabilized by complexation of the guest polymer, tert-butylanilid-PIBMA [210]...

Henriksen, J.R., and Ipsen, J.H. (2002) Thermal undulations of quasi-spherical vesicles stabilized by gravity. European Physical Journal E, 9 (4), 365-374. 

Vesicles Stabilized by Formation of Nonlipid Polymer Networks. .. 

Cationic vesicles typically used for DNA delivery often self-aggregate or bind to plasma proteins in vivo. Wu et al. [104] attempted to improve vesicle stability using a cationic lipid with a cross-linkable acrylamide attached to the headgroup (Fig. 16). Vesicles were polymerized using thermal initiation with AAPD. Compared to monomeric vesicles, polymerized vesicles were less cytotoxic, more resistant to aggregation in serum, and comparable in transfection activity using a vector encoding firefly luciferase. 

Fendler et al. [47] carried out experiments on vesicle-stabilized mixed crystals of Zn Cd. S and on CdS particles coated with ZnS. Besides absorption and fluorescence spectroscopy, x-ray diffractrometry was used for structural characterization of the various pure and mixed sulfide particles. In this article, the authors discuss thoroughly the fine interplay between kinetics and thermodynamics governing the rather complicated reaction scheme, finally yielding either separate particles of CdS and ZnS, mixed crystals Zn Cdj. S, or ZnS-coated particles of CdS. The latter may appear either as ZnS islands on the CdS particles or as a closed shell of ZnS surrounding a CdS core. In their experiments on capped particles, the authors of Ref. 47 do not attempt to decide which of the two morphologies occurs. 

The hydrogen-generation photo activity of vesicle-stabilized and catalyst-coated colloidal CdS was first demonstrated for dihexadecyl phosphate (DHP) vesicles with Rh as the catalyst and thiophenol (PhSH) as a sacrificial electron donor [see Fig. 5(a)] [4]. Although CdS could be located selectively at the inner or outer surfaces of the vesicles, the symmetrically organized systems were found to be the easiest to prepare most repro-ducibly. No significant effect of the CdS location on the photochemical activity for the H2 generation was observed. 

PolyiT1Grizabl6 CountGrions. Ion exchange of the coimterions of ionic lipids vs polymerizable coimterions such as choline methacrylate presents an additional route for vesicle stabilization much like the formation of the actin network of natural membranes. Photopolymerization yields vesicles with siuTace-associated polyelectrolytes. These vesicles were reported to have a similarly reduced permeability as polymerized mono-methacryloyl lipid vesicles (184). 

Self-organization of such amphiphilic block copolymers in aqueous solutions indicated the formation of vesicles. Stabilization of vesicles was attained by cross-linking chain extension of the PNIPAAm block using hexamethylene diacrylate [64]. Multifunctional micelles for cancer cell targeting, distribution, and anticancer drug delivery have been prepared using PNIPAAm-c )-methacrylic acid-g-PDLA and diblock copolymers [65]. 

To date there appear to be no equations available to describe the corresponding situation in vesicle systems. One reason for this is that the equilibrium state of vesicles is still not clearly established. Many systems are unstable and the usual transition is to return (by fusion of vesicles) to a lamellar state from which the vesicle system is often formed in the first place, which can be a very slow process. However, this is certainly not always the case. The problem of vesicle stability has been discussed in general terms by Luisi who suggests the following as some of the criteria for establishing whether or not a self-assembly system is at chemical equilibrium ... 

H.C. Youn, S. Bari, J.H. Fendler, Dihexadecyl phosphate, vesicle-stabilized and in situ generated mixed cadmium sulfide and zinc sulfide semiconductor particles preparation and utilization for photosensitized charge separation and hydrogen generation, J. Phys. Chem. 92 (1988) 6320-6327. 

Another well-characterized pH-sensitive liposome includes cholesterol hemisuccinate (CHEMS) as a stabilizer [97-100], and a carboxylated derivative of PE, A-succinyldioleoyl-PE, has been combined with DOPE to generate pH-sensitive liposomes [101]. pH-sensitive liposomes have been constructed using titrable double-chain glycerol-based amphiphiles as a PE vesicle stabilizer [102]. The pH-sensitive liposomes are stable at neutral or basic pH but are destabilized and become fusion competent at acidic pH. Eollowing the cellular uptake by an endocytic pathway, liposomes are exposed to a mildly acidic pH of endosomes, which is in the range of 5.0-6.5 [103,104]. 

---