Liposomes, bilayers

Srivastava A and Eisenthal K B 1998 Kinetics of molecular transport across a liposome bilayer Chem. Phys. Lett. 292 345-51... 

Kersten, G. F. A., Van de Put, A., Teerlink, T., Beuvery, E. C., and Crommelin, D. J. A. (1988a). Immunogenicity of liposomes and iscoms containing the major outer membrane protein of Neisseria gonorrhoeae -Influence of protein content and liposomal bilayer composition. Inf. Immun., 56. 1661-1664. 

The evaluation of the apparent ionization constants (i) can indicate in partition experiments the extent to which a charged form of the drug partitions into the octanol or liposome bilayer domains, (ii) can indicate in solubility measurements, the presence of aggregates in saturated solutions and whether the aggregates are ionized or neutral and the extent to which salts of dmgs form, and (iii) can indicate in permeability measurements, whether the aqueous boundary layer adjacent to the membrane barrier, Umits the transport of drugs across artificial phospholipid membranes [parallel artificial membrane permeation assay (PAMPA)] or across monolayers of cultured cells [Caco-2, Madin-Darby canine kidney (MDCK), etc.]. 

Virosomes are virus-mimicking systems that contain liposomal bilayer and pH-dependent protein impregnated in the liposomal wall. Virosomes are produced by a detergent dialysis procedure. Many researchers have demonstrated that the virosomes facilitate the leakage of the encapsulated drugs from the endosomes into the cytoplasm. This is, however, complicated technology and, so far, no virosome products are used in the clinical practice. 

However, since many of the traditional biotinylation reagents, such as NHS-LC-biotin contain hydrophobic spacers, their use with amphipathic liposomal constructions may not be entirely appropriate. A better choice may be to use a hydrophilic PEG-based biotin compound that creates a water-soluble biotin modification on the outer aqueous surface of the liposome bilayer. Biotinylation reagents of this type are discussed in Chapter 18, Section 3. 

Covalent attachment of proteins to the surface of liposomal bilayers is done through reactive sites created on the head groups of phospholipids with the intermediary use of a crosslinker or other activating agent. The lipid functional groups described in Section 1 of this chapter are modified according to the methods discussed in Section 2 to be reactive toward specific target... 

As lipophilic anchors, we chose modifications with long acyl and alkyl chains, preferably of similar chain lengths as the phospholipids to allow optimal alignment with the phospholipids molecules of the liposome bilayers. 

Zhang W, van Winden EC, Bouwstra JA, et al. Enhanced permeability of freeze-dried liposomal bilayers upon rehydration. Cryobiology 1997 35 277. 

Tyrosine-Related Protein-2 Peptide Incorporation in Liposomal Bilayer... 

Incorporation of greater peptide amounts into the liposomal bilayer is limited by the disturbance of the bilayer integrity by the peptide itself, the lipid composition, and the production process conditions. 

Figure 10.3 Enzymatic synthesis of poly(adenylic acid) in self-reproducing oleate liposomes (redrawn from Walde et al., 1994a). (a) The ADP penetrates (sluggishly) the liposome bilayer, (b) in the presence of polynucleotide phosphorylase, ADP is converted in poly(A), which remains entrapped in the liposome, (c) Polycondensation of ADP goes on simultaneously with the self-reproduction of liposomes (A is the membrane precursor, oleic anhydride, which, once added, induces the self-reproduction of liposomes S, surfactant, in this case oleate, which is the hydrolysis product of A on the bilayer E is polynucleotide phosphorylase).

Figure 10.6 The antitumoral camptothecin (CPT), a lipophilic drug extracted from the Chinese tree Camptotheca acuminata, can be incorporated into the liposome bilayer due to its lipophilic character. The CPT-containing liposomes are studied as antitumor drug formulations. (Modified from Stano et al 2004.)...

Recognition of amino acids has been attempted more frequently with receptors that are likewise zwitterionic in nature (compare 35). Some early studies include the transport of phenylalanine by a merocyanine dye through a liposomal bilayer [53]. Rebek s dicarboxylate-complexing cleft 9 (see Sect. 2) turned out to be a selective (though achiral) binder of trypthophane, phenylalanine, and tyrosine methyl ether [54]. A reasonable structure for a phenylalanine complex of 2 1 stoichiometry, as deduced from NMR studies, is schematically represented in formula 39 [55]. 

By inserting hydrophobic antiobesity compounds into the liposomal bilayers, marine phospholipids would boost the effect of the inserted hydrophobic antiobesity compounds. When marine phospholipids are served as liposomal drinks, they would be more effective than adding into solid foods or feeds. These facts were borne out by Okada et al. (2011). They carried out the following experiment. Brown seaweed (Undaria pinnatifida) lipid containing fucoxanthin (UL) encapsulated into scallop midgut gland phospholipids (PL) liposomes were prepared to see the promotional effect of marine phospholipid liposome on antiobesity. Animal model used in their study was 3-week-old male diabetic-obese... 

Liposomes are artificial structures composed of phospholipid bilayers exhibiting amphiphilic properties (chapter 12). In complex liposome morphologies, concentric spheres or sheets of lipid bilayers are usually separated by aqueous regions that are sequestered or compartmentalized from the surrounding solution. The phospholipid constituents of liposomes consist of hydrophobic lipid tails connected to a head constructed of various glycerylphosphate derivatives. The hydrophobic interaction between the fatty acid tails is the primary driving force for creating liposomal bilayers in aqueous solutions. 

Similar to hydrophilic flavonoids, hydrophobic flavonoids can affect membrane permeability. Alterations in this biophysical property of liposome bilayers lead to the release of bulky molecules entrapped into the inner aqueous space. As mentioned in the previous section, a strong correlation was found between flavonoid retention to a hydrophobic matrix and their capacity to induce membrane leakage [Ollila et al., 2002]. Interestingly, hydrophilic flavonoids, such as (—)-epicatechin and related procyanidins (dimer to hex-amer) prevented Fe2 + -mediated liposome permeabilization, although in this case the beneficial effect could be related to both their antioxidant and metal chelating capacities and their membrane stabilizing properties [Verstraeten et al., 2004],... 

Hydrolysis is the other important mechanism for some lipids (glycerides and phosphoglycerides) to degrade. Lowering of pH can arise from both hydrolysis and lipid peroxidation (Arakane et al., 1995), as both processes can give acid products. It has also been reported that hydrolysis and peroxidation can act in synergy with one another in liposome bilayers (Swern, 1995), but it is uncertain whether this can happen for other structures since different mechanisms are operative for... 

Early in the development of liposomes, it was recognized that their plasma instability could be a serious detriment in certain applications. Consequently, there were efforts to Lrst incorporate polymerizable lipids into the liposomal bilayers, and then initiate polymerization by, for example, photolysis, to form interchain crosslinks to stabilize the bilayer. The most commonly used polymerizable lipids have been PCs-containing diacetylene or butadiene moieties in the tailgroups... 

Although not strictly within the scope of this chapter, a few other delivery systems are worth mentioning by virtue of their similarity to liposomes. Bilayer vesicle structures are not limited to phospholipids. For example, cholesterol hemisuccinate vesicles have been proposed as a deliver system for poorly soluble substances (Janoffet al., 1988). Similarly, an Amphotericin B/cholesterol... 

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