Liposome deformation

Liposome Deformation by Imbalance of pH and Ionic Strength Across the Membrane... 

We will show below the results of the deformations for liposome after exchanging the outer solution various at pH and I.S, and results of ti-A isotherms for DOPC monolayers on MES buffer solutions with their pH and Ionic strength. The results of the liposome deformation were discussed based on the results of ti-A isotherms. First, we confirmed that no significant deformation of liposome was observed when exchanging the outer solution from ultra pure water to the MES buffer with pH 5.6 and ionic strength 0.001. 

Figure 2(a) shows behavior of the liposomes after exposure to the MES buffer with pH 3.5 and ionic strength 0.001. The liposomes kept their shape for 5 min into the exposure, after which time the membrane buckled and folded in on itself, resulting in small inward protrusions within the stiU-spherical, yet smaller liposome. These deformations at created by pH gradients across the membrane surfaces suggests that liposomes deform not only by osmotic pressine differences. 

Figure 1 (a) Fluorescence microscope images of DOrc liposomes after exposure to solutions of MES buffer with pH 5.6 and ionic strength 0.6, accompanied by illustrations of the corresponding liposome deformations for each time. The times below the images display the elapsed time since the liposomes were exposed to the selected buffer, (b) ti-A isotherms for DOPC monolayers over MES buffers with pH 5.6 and ionic strength 0.6 (solid curve) or with pH 5.6 and ionic stength 0.001 (dashed curve)... 

Transfersomes, deformable liposomes, were introduced by Cevc et al. in the early 1990s [66-69]. The main components of these systems are phospholipids, a surfactant edge activator (such as sodium cholate), water and sometimes very low concentrations of ethanol (<7%) [66]. Transfersomes are prepared by the same methods as liposomes. The preparation process is usually followed by homogenization, sonication, or other mechanical means to reduce the size of the lipid vesicles. 

El Maghraby, G.M., A.C. Williams, and B.W. Barry. 1999. Skin delivery of oestradiol from deformable and traditional liposomes Mechanistic studies. J Pharm Pharmacol 51 1123. 

Figure 3 Possible mechanisms of MS channel activation by bilayer deformation forces. Hydrophobic mismatch and bilayer curvature are considered as deformation forces of pressure-induced changes in the lipid bilayer causing conformational changes in MS channels as indicated by the example of MscL (13). These changes were studied experimentally by reconstituting purified MscL proteins in liposome bilayers prepared from synthetic phosphatidylcholine lipids of well-defined composition. The changes in functional properties were examined by the patch-clamp technique, whereas the structural changes were determined by EPR and FRET spectroscopy. (Reproduced from Reference 12, with permission).

Same laser for Raman and one optical tweezers 730 nm Synaptosomes CH2 deformation at 1,445 cm Amide I at 1,657 cm Synaptosomes isolated from rat brain neurons dispersed in buffer solution. Appearing beads reveal that synaptosomes include liposomes and proteins... 

During recent years, the topical delivery of liposomes has been applied to different applications and in different disease models (188). Current efforts in this area concentrate around optimization procedures and new compositions. Recently, highly flexible liposomes called transferosomes that follow the trans-epidermal water activity gradient in the skin have been proposed. Diclofenac in transferosomes was effective when tested in mice, rats and pigs (189). The concept of increased deformability of transdermal liposomes is supported by the results of transdermal delivery of pergolide in liposomes, in which elastic vesicles have been shown to be more efficient (190).The combination of liposomes and iontophoresis for transdermal delivery yielded promising results (191, 192). 

The deformability of elastic liposomes is determined by assessment of the extrusion of the suspension through a filter membrane of defined pore size (50 nm) under pressure (24, 31). The amount of liposome suspension extruded is measured and the liposome size and shape are determined as previously described. For each liposome suspension, the mean standard deviation of... 

Trotta M, Peira E, Carlotti ME, Gallarate M (2004) Deformable liposomes for dermal administration of methotrexate. Int J Pharm 270(1-2) 119-125... 

Elsayed MM, Abdallah OY, Naggar VF, KhalafaUah NM (2006) Deformable liposomes and ethosomes mechanism of enhanced skin deUvery. Int J Pharm 322(I-2) 60-66... 

The acidification of endosomal compartments, as they evolve toward lysosomes is a well-described phenomenon (1) that can be exploited to design drug delivery systems capable of releasing their contents after endocytosis. Enhanced cytoplasmic drug concentrations can therefore be achieved with smart formulations, which are sensitive to acidic pHs. For this purpose, liposomal formulations are attractive, because their deformable phospholipid bilayers can be rapidly disrupted to trigger drug release. In this section, ionizable copolymers of ISTisopropylacrylamide (NIPAM) are anchored in the phospholipid membrane and used to destabilize the bilayer upon acidification of the environment. 

It is useful, for reasons which are apparent in relation to movement of nanoparticles in vivo, to divide nanosystems into two types, hard and soft, although there are obviously intermediate situations. Hard systems, for example, polymeric nanoparticles and nanocapsules, nanosuspensions or nanocrystals, dendrimers, and carbon nanotubes are neither flexible nor elastic. Hard systems can block capillaries and fenestrae that have dimensions similar to the particles, whereas soft systems can deform and reform to varying degrees. Erythrocytes and many liposomes fall into this category and are thus better able to navigate capillary beds and tissue extracellular spaces. Soft systems include nanoemulsions (microemulsions) and polymeric micelles. 

The potential of polymersomes in biomedical applications have been extensively discussed in several reviews [19,22-26], so they are mentioned here only briefly. Mainly due to the high molecular weight of their amphiphiles they differ from liposomes in several aspects, which makes them beneficial for certain purposes. (1) Typically, they have a much thicker shell. For the vesicles shown in Fig. 2c the hydrophobic core thickness is d = 21 nm, while for lipid membranes typically dm 3 nm. (2) Due to the larger thickness, polymeric membranes are much less susceptible to fluctuations and defects, and they can withstand larger deformations than lipid systems. It is remarkable that, while lipid bilayers can be stretched only 5%... 

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