Hydrophobically modified, interaction with liposomes

Interactions of Hydrophobically Modified Poly(A -Isopropylacrylamides) with Liposomes Fluorescence Studies... 

These preliminary microcalorimetric measurements suggest that there is apparently no interaction between the homopolymer and the liposomes, since the LCST transition is unaffected by the presence of liposomes. However the signal corresponding to the LCST of the hydrophobically-modified polymers is altered in the presence of liposomes, in terms of both intensity and broadness. This observation is taken as a clue that these polymers interact with the liposomes. Particularly revealing is the fact that for liposomes in their fluid state (DMPC) an LCST transition can still be detected, but this transition seems to disappear for liposomes in their solid-analogous state (DSPC). This dependence of the polymer/liposome interactions on the membrane phase will be put on much firmer grounds by the fluorescence experiments described next. Indeed further microcalorimetric measurements with fully coated liposomes systems need to be... 

We can rationalise these differences assuming that when in liposomal complex, the apoHBD interacts with the polar head and with the proximal part of the hydrophobic chains (may be up to 4-6 carbon atoms) which is the region less modified by the gel-to-liquid-crystalline phase transition (Hubbell Me Connell, 1970 Levine et al., 1972 Barton Gunstone, 1975) therefore the enzyme-liposome interaction and, consequently, the HBD activity of these complexes is not sensitive to phase transitions. Conversely, in the diC14 substituted membranes (and may be in the original mitochondria) the apoHBD could be deeply inserted in the lipid matrix and would... 

Another method to improve the incorporation of bioactive polymers into the cells is the grafting of hydrophobic groups on the polymer, which improves the affinity for the cell membrane. Maleic copolymers are good candidates for such modifications, the anhydride cycle being easily reacted with hydrophobic amines. Poly(MA-St), poly(MA-CDA) and poly(maleic anhydride-alt-3,4-dihydroxyphenylprop-l-ene) modified with alkyl amines or aniline were proved to perturb the liposome membrane and to interact with epithelial cells or DMSO-differentiated HL-60 cells [48-50]. As a result, the biological activity, evaluated by the ability to simulate the release of superoxide anion by the cells, was enhanced when the polymer was modified with hydrophobic units [49]. 

Insertion of modified receptors into liposomal bilayers. Bilayers of liposomes consist of phospholipid assemblies that hold individual Upid molecules by weak van der Waals forces. Ligands or receptors with surface-active groups can be inserted into liposomal bilayers (Fig. 5c). Proteinaceous receptors are usually nonamphiphilic, and hence they can be modified with alkyl chains or lipids that can be positioned along the hydrophobic part of bilayers. Then the relatively hydrophilic receptor part is exposed to the liposomal surface and can interact with ligands of cell surfaces [37,38]. 

The surfaces of liposomes have been coated [17] with thermosensitive pol5uners such as poly(A -isopropylacrylamide) [poly(NIPAM)] by taking advantage of the phase transition of polymers. The molecular structure of a hydrophobically modified poly(NIPAM), which has been studied in the preparation of temperature-sensitive Uposomes [17], is depicted in Fig. 7. Poly(NlPAM) exhibits a low critical solution temperature (LCST) around 32°C, and the LCST can be altered toward the body temperature by co-pol5unerization [56], The pol5uner is in an expanded form at low temperature, but above the critical temperature it is in a contracted form. The interactions of SUVs and hydrophobically modified poly(NIPAM) were studied by fluorescence spectroscopy [88]. More recently, sonicated DPPC and egg PC Uposomes coated with a copolymer of NIPAM and octadecylacrylate in a molar ratio of 100 1 were prepared [17,89], It was shown that above the LCST of the copolymer, the release of calcein and carboxyfluorescein from... 

Electrochemistry may also be used to probe the interactions between ferrocifens and nonpolar molecular architectures, with respect to the hydrophobic architectures/barriers that compose ceU membranes as well as lipidic cargoes/vectors (e.g., liposomes) using model systems consisting of glassy carbon electrodes modified with a planar bilayer of 1,2-dimyristoyl-OT-glycero-3-phosphocholine (DMPC) (Fig. 47.20) [56]. 

Since the tethered polymer chain changes its character between hydrophilic and hydrophobic near the LCST of the polymer, the polymer-modified liposomes are expected to reveal its affinity to cell surfaces differently, depending on temperature. We prepared EYPC Uposomes modified with copoly(APr-NIPAM)-2C 12, which exhibits the LCST near the physiological temperature. Temperature-dependent interaction of the thermosensitive polymer-modified liposomes with CVl cells, an Afriean green monkey kidney cell line, is described. 

The present study demonstrated that interactions of the thermosensitive polymer-modified liposomes with model membranes and cells were suppressed by the hydrated polymer chains attached to the liposome surface below the LCST. However, the hydrophilic-to-hydrophobic change of the tethered polymer chains above the LCST enhanced their interactions. As a... 

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