Methacryloylic lipids

The polymerization of the butadiene monomers (3,4) can also be followed spectroscopically by the disappearance of the strong absorption of the monomers at 260 nm, whereas the absorption of the resulting poly-1,4-trans(butadiene)s is too small to be observed in a single monolayer. The polymers from the butadiene and methacryloyl lipids are probably better model membrane systems, because the polymer chains are still mobile and not excessively rigid as the polydiacetylenes. 

Polymer formation from monomeric butadiene lipid vesicles is demonstrated by the decrease of the monomer absorption at 260 nm as well as by GPC of the residue of a freeze dried polymer vesicle dispersion. The latter method was also used for proving the formation of polymeric vesicles from the methacryloyl lipids. 

The permeability of solutes across lipid bilayers is a product of the partition coefficient and the transverse diffusion coefficient [30]. Bilayer polymerization can alter solute diffusion by modifying either or both of these processes. In order to examine the effect of polymerization on bilayer permeability a nonionic solute of moderate permeability, [3H-glucose], was encapsulated in the vesicles prior to polymerization, removed from the exterior after polymerization, and its permeation across the bilayer was measured periodically [31]. Quantitative measurements of the 3H-glucose leakage revealed that the formation of linear polymer chains from methacryloyl lipids reduced the permeability coefficient to 0.3 to 0.5 of that of the unpolymerized lipid vesicles. A larger reduction (two orders of magnitude) was only found when crosslinked polymer networks were formed [31]. 

An even more striking effect is observed by addition of the surfactant sodiumdodecyl sulfate (SDS) to vesicles (Fig. 23). While monomeric vesicles of (19) and dipalmitoylle-cithin are destroyed by low SDS concentrations, the polymerized vesicles are stable up to 2 - 10 3 mol/1 SDS25). Polymerized vesicle dispersions can be diluted with ethanol without precipitation.231 Polymeric liposomes of (20) are stable in 80% ethanol for weeks. This could also be shown by Regen et al. for polymerized vesicles of the methacryloylic lipids (4) and (6)13141 (Fig. 24) by monitoring the turbidity (absor-... 

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). 

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). 

On the contrary, butadiene and methacryloyl monomers (1,3,4, 10,11) can also be polymerized in the liquid expanded phase. The butadiene lipids have previously been shown to form 1,4-trans-poly(butadiene)s (40j in the monolayer (Eqn. II.). 

All four types of polymerizable lipids shown in Fig. 4 have been realized synthetically. In this context, one need not attempt to reproduce mother nature slavishly (Fendler 8)). Kunitake 9) was able to show that simple molecules like dialkyldimethyl-ammonium salts also form bilayer assemblies. Fuhrhop 10) and Kunitake U) could accomplish the formation of monolayer liposomes with molecules containing only one alkyl chain and two hydrophilic head groups. Acryloylic and methacryloylic groups (type a and d, Table 1), as well as diacetylenic, butadienic, vinylic and maleic acid groups (type b and c), have been used as polymerizable moieties. A compilation of amphiphilic, photopolymerizable molecules is given in Table 1. 

In contrast to the topochemically polymerizable diacetylenes, methacryloylic and butadienic lipids are also polymerizable in the liquid like phase. Figure 11 shows the contraction behavior of butadiene lecithin (19) during irradiation in the liquid analogous state 22). The final polymer has a 1,4-trans structure22). 

Compared to diacetylenes, methacryloylic and butadienic lipids exhibit a higher mobility of their polymer chains, and therefore, are more suitable for the formation... 

In the case of butadienic lipids, the polyreaction was followed by a decrease of the strong monomer absorption (260 nni)25). Disappearance of vinyl protons in the 2H NMR spectrum proved polymer formation for vesicles made from vinylic, acryloylic, and methacryloylic surfactants l3,16). 

K. Dorn 105 > polymerized dialkylammonium lipids with the polymerizable methacryloyl moiety either in the head group (29) or at the end of one of the hydrophobic chains (5). GPC revealed Mw 1.9 x 106, Mn 3.5 x 105, Mw/Mn 5.4 for (29) and Mw 1.9 xl06,Mn 3.9 x 105, Mw/Mn 2.4 for (5). It was also found that Mw varies inversely with the time of sonication, i.e. in smaller liposomes lower-molecular-weight polymers are formed. In a following paper, K. Dorn 108 present data for the permeability of monomeric and polymeric vesicles from (29). 

Figure 19.3. Structures of some polymerizable lipids with butadiene (4), methacryloyl (5),...

In pursuit of enhanced liposomal stability, Ringsdorf, Regen, Chapman, and O Brien pioneered the use of polymerized liposomes. These liposomes were prepared from polymerizable lipid molecules. Polymerized liposomes demonstrated uniform size distribution and are considerably more stable compared to their unpolymerized counterparts. Various polymerizable groups (e.g., butadiene, dia-cetylene, vinyl, or methacryloyl ) have been used to achieve the polymerization of the lipid bilayers. These reactive groups on the lipid may be in the head group region, the hydrocarbon core, or at the hydrocarbon termini. 

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