Amphiphilic polymers with liposomes

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... 

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].

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 . ... 

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. 

In summary, the fluorescence experiments and the microcalorlmetric measurements provide strong evioence for the following description of the interactions between amphiphilic NIPAM copolymers and liposomes 1. the polymeric micellar structures formed in water are disrupted irreversibly when they enter in contact with liposome surfaces 2. polymer chains reorganize on the surface of the vesicle in a slow... 

On the contrary, amphiphilic block copolymers can form various vesicular architectures in solution— a nanometer-sized structure with a double-layer outer membrane that encloses an inner volume, known as polymer-based liposomes (polymersomes). These include uniform common vesicles, large polydisperse vesicles, entrapped vesicles, or hollow concentric vesicles. Examples in this context are vesicles based on poly(ethylaie oxide)-fc-poly(ethylene) (PEO-fc-PE) and poly(ethylene oxide)-h-polybutadiene (PEO-fc-PB) block copolymers, with various block compositions (Lee et aL 2(X)1). 

Moreover, nanoprecipitation has been used for the preparation of polymersomes and nanocapsules. Polymersomes are a new class of vesicles, which were inspired by phospholipids that self-assembled in liposomes. They have been obtained by nanoprecipitation using amphiphilic diblock copolymers. Polymersome showed higher stability and lower permeability of the shell compared to viral capsids. Polymersomes were loaded with doxorubicin using co-precipitation and were used to deliver drugs to breast cancer cells [71-73]. Nanocapsules were formed by dissolving the solution of polymer with a small amount of oil and an active compound in water. Precipitation of the hydrophobic polymer on the surface of oil droplets leads to the formation of core shell nanocapsule [9]. 

The most versatile method to prepare such hollow capsules is self-assembly [203-205, 214, 215]. Owing to their amphiphilic nature and molecular geometry, lipid-based amphiphiles can aggregate into spherical closed bilayer structures in water so-called liposomes. It is quite reasonable that the hollow sphere structure of liposomes makes them suitable as precursors for the preparation of more functional capsules via modification of the surfaces with polymers and ligand molecules [205, 216, 217]. Indeed, numerous studies based on liposomes in this context have been performed [205, 209, 213]. 

To increase the load of liposomes and micelles with reporter metals, we designed a new family of amphiphilic single-terminus modified polymers containing multiple chelating groups that could be incorporated into the hydrophobic domains of liposomes and micelles. The approach is based on the use of CBZ-protected polylysine (PL) with a free terminal amino group, which is derivatized into a reactive form with subsequent deprotection and incorporation of DTPA residues. This was initially suggested by us for heavy metal load on proteins and antibodies [17]. 

Arnold and co-workers attempted to prepare imprinted metal-coordinating polymers for proteins [25]. For this purpose, efforts were made to prepare metalcoordinating molecularly patterned surfaces in mixed monolayers spread at the air-water interface or liposomes. This approach was termed as molecular printing and is illustrated in Fig. 6.6. In this process, a protein template is introduced into the aqueous phase, which imposes a pattern of functional amphiphiles in the surfactant monolayer via strong interactions with metal-chelating surfactant head groups. The pattern is then fixed by polymerising the surfactant tails. The technique has also been employed for two dimensional crystallisation of proteins [26]. 

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