Vesicles polymerizable

The scientific community was attracted to the study of liposomes due to the relatively simple procedure of their preparation. Moreover, if prepared from natural phospholipids, they are biocompatible, and possess low cytotoxicity, low immunogenicity, and biodegradability [304], Liposomes, however, have two main disadvantages the structural instability both in vitro and in vivo, and low cell specificity [304], To increase the stability, the structure of the phospholipid layer has been modified to include artificial lipids and/or cholesterol. Polymerizable vesicles have also been prepared [305]. It is obvious that the biocompatibility of these modified systems has to be addressed. 

Electric field-induced fusion has been applied to a vast variety of cells including human erythrocytes and liposomes made from asolectin and egg phosphatidylcholine. To what extent this method can be utilized for fusing polymerizable vesicles will be demonstrated in the following. 

Besides this "s3mthetic route, the combination of natural and polymerizable membrane components is principally possible via the fusion of cell membranes with polymerizable vesicles. Fusion of cells is possible using dielectrophoresis and dielectric breakdown. Since it was possible to prepare giant" vesicles (visible under the light microscope) these techniques were also successfully applied to vesicle-vesicle fusion. Investigations on cell-vesicle fusion are currently under way. 

Before trying to fuse polymerizable vesicles with natural cells, investigations on vesicle-vesicle fusion are necessary. A very selective fusion method recently described by Zimmermann (35) was applied to these fusion experiments. 

Figure 5.6. Typical structures of polymerizable vesicle-forming surfactants (a) terminal unsaturation in the tail (b) internal unsaturation in the tail (c) unsaturation associated with the head group.

While most vesicles are formed from double-tail amphiphiles such as lipids, they can also be made from some single chain fatty acids [73], surfactant-cosurfactant mixtures [71], and bola (two-headed) amphiphiles [74]. In addition to the more common spherical shells, tubular vesicles have been observed in DMPC-alcohol mixtures [70]. Polymerizable lipids allow photo- or chemical polymerization that can sometimes stabilize the vesicle [65] however, the structural change in the bilayer on polymerization can cause giant vesicles to bud into smaller shells [76]. Multivesicular liposomes are collections of hundreds of bilayer enclosed water-filled compartments that are suitable for localized drug delivery [77]. The structures of these water-in-water vesicles resemble those of foams (see Section XIV-7) with the polyhedral structure persisting down to molecular dimensions as shown in Fig. XV-11. 

An extraordinary way of stabilizing RUO2-coated CdS colloids for H2 generation was chosen by Fendler and co-workers The colloidal particles were generated in situ in surfactant vesicles of dioctadecyldimethylammonium chloride and dihexa-decyl phosphate. Thiophenol as a membrane permeable electron donor acted as a sacrificial additive. Later, a surface active re-usable electron donor (n-C,gH3,)2N — (CHj)—CH2—CHj—SH, Br was incorporated into the vesicles. Its R—SS—R oxidation product could be chemically reduced by NaBH to regenerate the active electron donor. The H2 yields in these systems were only 0.5 %. However, yields up to 10% were later reported for a system in which CdS was incorporated into a polymerizable styrene moiety, (n-C,jH3jC02(CH2)2) N (CH3) (CH2CgH4CH=CH2>, CP, and benzyl alcohol was used as the electron donor. 

A novel polymerized vesicular system for controlled release, which contains a cyclic a-alkoxyacrylate as the polymerizable group on the amphiphilic structure, has been developed. These lipids can be easily polymerized through a free radical process. It has been shown that polymerization improves the stabilities of the synthetic vesicles. In the aqueous system the cyclic acrylate group, which connects the polymerized chain and the amphiphilic structure, can be slowly hydrolyzed to separate the polymer chain and the vesicular system and generate a water-soluble biodegradable polymer. Furthermore, in order to retain the fluidity and to prepare the polymerized vesicles directly from prev lymerized lipids, a hydrophilic spacer has been introduced. 

Several workers have introduced polymerizable groups into twin-tailed amphiphiles and formed vesicles by sonication. They then link the amphi-philes by initiating polymerization, either chemically or photochemically. The polymerized vesicles which are so generated show little tendency to fuse, and are much more stable than the vesicles formed by sonication or vaporization. They therefore have considerable potential for compartmentalizing reagents, although as with normal vesicles there is always the... 

One approach could be the attempt to include the lipids into the stabilization process. Lipid molecules bearing polymerizable groups can actually be arranged as planar monolayers or as spherical vesicles and polymerized by high energy irradiation within these membrane like structures under retention of the orientation of the molecules (8,9,36). 

These molecular assemblies are unfortunately not stable enough to construct practical solar energy conversion systems. Vesicles composed of polymerizable monomers (e.g., 4, 5) were polymerized to give polymeric vesicles having enhanced stability 25 26). 

A similar study by O Brien and coworkers utilized bilayers composed of a shorter chain diacetylenicPC (9) and DSPC or DOPC [37]. Phase separation was demonstrated in bilayers by calorimetry and photopolymerization behavior. DSC of the 9/DSPC (1 1) bilayers exhibited transitions at 40 °C and 55 °C, which were attributed to domains of the individual lipids. Polymerization at 20 °C proceeded at similar rates in the mixed bilayers and pure 9 bilayers. A dramatic hysteresis effect was observed for this system, if the bilayers were first incubated at T > 55 °C then cooled back to 20 °C, the DSC peak for the diacetylenicPC at 40 °C disappeared and the bilayers could no longer be photopolymerized. The phase transition and polymerizability of the vesicles could be restored simply by cooling to ca. 10 °C. A similar hysteretic behavior was also observed for pure diacetylenicPC bilayers. Mixtures of 9 and DOPC exhibited phase transitions for both lipids (T = — 18 °C and 39 °C) plus a small peak at intermediate temperatures. Photopolymerization at 20 °C initially proceeded at a similar rate as observed for pure 9 but slowed after 10% conversion. These results were attributed to the presence of mixed lipid domains... 

In 1985 Tyminski etal. [55, 56] reported that two-component lipid vesicles of a neutral phospholipid, e.g. DOPC, and a neutral polymerizable PC, bis-DenPC (15), formed stable homogeneous bilayer vesicles prior to photopolymerization. After photopolymerization of a homogeneous 1 1 molar lipid mixture, the lipid vesicles were titrated with bovine rhodopsin-octyl glucoside micelles in a manner that maintained the octyl glucoside concentration below the surfactant critical micelle concentration. Consequently there was insufficient surfactant to keep the membrane protein, rhodopsin, soluble in the aqueous buffer. These conditions favor the insertion of transmembrane proteins into lipid bilayers. After addition and incubation, the bilayer vesicles were purified on a... 

SUVs have also been stabilized by coating their outer surfaces with chitin [328], polylysine [329-332], polyelectrolytes [333], and polysaccharides [334]. Advantage has also been taken of electrostatic interactions to attract oppositely charged polyelectrolytes to outer SUV surfaces and subsequently polymerize them in situ [335-339]. These systems have been referred to as liposomes in a net [72]. A particularly telling example is the attachment of a two-dimensional polymeric network either to the inner or to the outer surfaces of SUVs by ion exchanging the vesicle counterions with oppositely charged polymerizable short-chain counterions and their subsequent polymerization (Fig. 42) [340-342]. 

Fig. 42. Preparation of vesicle membranes with asymmetrically or symmetrically bound polyelectrolytes from lipids with polymerizable counterions [340]. GPC = gel permeation chromatography [72]...

Aqueous dispersions of polymerizable lipids and surfactants can be polymerized by UV irradiation (Fig. 18). In the case of diacetylenic lipids the transition from monomeric to polymeric bilayers can be observed visually and spectroscopically. This was first discussed by Hub, 9) and Chapman 20). As in monomolecular layers (3.2.2) short irradiation brings about the blue conformation of the poly(diacetylene) chain. In contrast, upon prolonged irradiation or upon heating blue vesicles above the phase transition temperature of the monomeric hydrated lipid the red form of the polymer is formed 23,120). The visible spectra of the red form in monolayers and liposomes are qualitatively identical (Fig. 19). 

Methacryloylic lipid (5) is polymerizable in the hydrophobic part of the molecule. The phase transition temperature of the polymeric vesicle is again lowered compared to the non-polymerized vesicle (Fig. 27). The difference between the phase transition temperatures of monomer and polymer is somewhat larger than in the case of acrylamide (29). This might indicate that a saturated polymer chain in the hydrophobic core of a membrane decreases membrane order to a higher extent than a polymer chain on the membrane surface 15). 

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