Amphiphilic polymers with membranes

Diacyllipid-polyethyleneoxide conjugates have been introduced into the controlled drug delivery area as polymeric surface modiLers for liposomes (Klibanov et al., 1990). Being incorporated into the liposome membrane by insertion of their lipidic anchor into the bilayer, such molecules can ster-ically stabilize the liposome against interaction with certain plasma proteins in the blood that results in signiLcant prolongation of the vesicle circulation time. The diacyllipid-PEO molecule itself represents a characteristic amphiphilic polymer with a bulky hydrophilic (PEO) portion and a very short but extremely hydrophobic diacyllipid part. Typically, for other PEO-containing amphiphilic block... 

This subject can be considered in terms of five different types of molecules or materials (a) biologically inert, water-insoluble polymers (b) water-insoluble polymers that bear biologically active surface groups (c) water-swellable polymeric gels, or amphiphilic polymers that function as membranes (d) water-insoluble but bioerodable polymers that erode in aqueous media with concurrent release of a linked or entrapped bioactive molecule and (e) water-soluble polymers that bear bioactive agents as side groups. 

C. Tribet, R. Audebert, J.-L. Popot (1997) Stabilisation of hydrophobic colloidal dispersions in water with amphiphilic polymers application to integral membrane proteins. Langmuir, 13 5570-5576... 

Figure 1 Schematic structures of micelle and liposome, their formation and loading with a contrast agent, (a) A micelle is formed spontaneously in aqueous media from an amphiphilic compound (1) that consists of distinct hydrophilic (2) and hydrophobic (3) moieties. Hydrophobic moieties form the micelle core (4). Contrast agent (asterisk gamma- or MR-active metal-loaded chelating group, or heavy element, such as iodine or bromine) can be directly coupled to the hydrophobic moiety within the micelle core (5), or incorporated into the micelle as an individual monomeric (6) or polymeric (7) amphiphilic unit, (b) A liposome can be prepared from individual phospholipid molecules (1) that consists of a bilayered membrane (2) and internal aqueous compartment (3). Contrast agent (asterisk) can be entrapped in the inner water space of the liposome as a soluble entity (4) or incorporated into the liposome membrane as a part of monomeric (5) or polymeric (6) amphiphilic unit (similar to that in case of micelle). Additionally, liposomes can be sterically protected by amphiphilic derivatization with PEG or PEG-like polymer (7) [1].

Hydrophobically modified polybetaines combine the behavior of zwitterions and amphiphilic polymers. Due to the superposition of repulsive hydrophobic and attractive ionic interactions, they favor the formation of self-organized and (micro)phase-separated systems in solution, at interfaces as well as in the bulk phase. Thus, glasses with liquid-crystalline order, lyotropic mesophases, vesicles, monolayers, and micelles are formed. Particular efforts have been dedicated to hydrophobically modified polyphosphobetaines, as they can be considered as polymeric lipids [5,101,225-228]. One can emphasize that much of the research on polymeric phospholipids was not particularly focused on the betaine behavior, but rather on the understanding of the Upid membrane, and on biomimicking. So, often much was learnt about biology and the life sciences, but little on polybetaines as such. 

Prepolymerized lipids form vesicles only if the disentanglement of the polymer main chain ( = hack hone) and the membrane forming side-chains is simplified hy a hydrophilic spacer between them . Efficient decouplings of the motions of the polymeric chain and the polymeric bilayer are thus achieved and stable liposomes with diameters of around 500 nm were formed upon ultrasonication (Figure 4.28a). Their bilayer showed a well-defined melting behaviour in DSC. The ionene polymer with C12, C16 and C20 intermediate chains also produced vesicles upon sonication (Figure 4.28b). Here, the amphiphilic main chain is obviously so simple that ordering to form membranes produces no problems whatsoever . ... 

Artificial enzymes may be divided into two categories semisynthetic artificial enzymes and synthetic artificial enzymes. Semisynthetic artificial enzymes are partly prepared by biological systems. Catalytic antibodies are typical examples of semisynthetic artificial enzymes. Semisynthetic artificial enzymes are also prepared by modification of a known protein or enzyme at a defined site with a cofactor or new functional group. Synthetic artificial enzymes are prepared totally by synthetic methods. Synthetic artificial enzymes may be either relatively small molecules with well-characterized structures or macromolecules. The term syn-zymes has been coined to designate synthetic polymers with enzyme-like activities. In addition, synthetic artificial enzymes are also obtained with molecular clusters such as micelles and bilayer membranes formed by amphiphiles. 

Fig. 2 The construction of a polymer-cushioned lipid bilayer membrane. (A) Architecture constructed in a sequential way first, onto the functionalized substrate a polymer layer (cushion) is deposited by adsorption from solution and covalent binding, followed by the (partial) covalent attachment of a lipid monolayer containing some anchor lipids as reactive elements (B) able to couple the whole monolayer to the polymer cushion. (C) Alternatively, a lipopolymer monolayer, organized, e.g., at the water-air interface can be co-spread with regular low-mass amphiphiles and then transferred as a mixed monolayer onto a solid support, prefunctionalized with reactive groups, able to bind covalently to the polymer chains of the lipopolymer molecules, (B). (D) By a fusion step (or a Langmuir Schaefer transfer) the distal lipid monolayer completes the polymer-tethered membrane architecture...

Besides cells, cell organelles and cellular vesicles are also surrounded by membranes, which are composed of a double layer formed by amphiphilic molecules. These amphiphiles are mostly phospholipids and therefore the resulting vesicles are called liposomes. Similarly, amphiphilic polymers can form a lipid-like double layer that forms the membrane of a polymeric vesicle, the so-called polymersome [4]. In contrast to micelles, the inner and outer parts of the membrane of polymersomes are in contact with water. 

One interesting aspect of amphiphilic macromolecules is their interactions with phospholipid membranes, natural or artificial. Also amphiphilic in their chemical nature, phospholipid building blocks change their supramolecular ordering by incorporating amphiphilic polymers within their membrane assemblies. Depending on structural and compositional factors, various membrane deformations such as pore or tube formation, or complete disruption have been reported (34-40). In this respect, biological activities of amphiphilic... 

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