Cholesterol liposomes content

The fate of injected liposomes is drastically altered by administration route, dose and size, lipid composition, surface modification, and encapsulated drugs. Liposomes encapsulating drugs are often administered iv, therefore, the stability of liposomes in plasma is important. When liposomes composed of PC with unsaturated fatty acyl chains are incubated in the presence of serum, an efflux of internal solute from the liposomes is observed. This increase in permeability is caused by the transfer of phospholipids to high density lipoprotein (HDL) in serum (55). To reduce the efflux of liposomal contents, cholesterol is added as a liposomal component... 

Fluorometric and spectrophotometric studies of filipin-cholesterol interaction showed that the stoichiometry of the interaction was 1 1 [150] or 1 1.5 [146,147]. UV spectrophotometry changes have been used to monitor the stoichiometry of the interaction between filipin and free or liposome-bound cholesterol. Analysis of aqueous dispersions suggested that the stoichiometry was 1 1 [171]. Lecithin, dicetyl phosphate-cholesterol liposomes only produced maximal spectral changes of filipin when the sterol polyene ratio was 1 1 [172]. Filipin released trapped ion markers from sterol—phospholipid liposomes. The rate of release was dependent upon cholesterol content of the liposome membrane (maximum at sterol phospholipid ratio of 1 1) and upon the molar fllipin sterol ratio (maximum at fllipin sterol ratio of 1 1). 

Boomer JA, Qualls MM, Inerowicz HD, Haynes RH, Patri VS, Kim J-M, Thompson DH (2009) Cytoplasmic delivery of liposomal contents mediated by an acid-labile cholesterol-vinyl ether-PEG conjugate. Bioconjugate Chem 20 47-59... 

An important question arises about the effects of phospholipid composition and the function of membrane-bound enzymes. The phospholipid composition and cholesterol content in cell membranes of cultured cells can be modified, either by supplementing the medium with specific lipids or by incubation with different types of liposomes. Direct effects of phospholipid structure have been observed on the activity of the Ca2+-ATPase (due to changes in the phosphorylation and nucleotide binding domains) [37]. Evidence of a relationship between lipid structure and membrane functions also comes from studies with the insulin receptor [38]. Lipid alteration had no influence on insulin binding, but modified the kinetics of receptor autophosphorylation. 

Figure 3 Molecular relaxivities of liposomes with different Gd-containing membranotropic chelators. Liposomes (egg lecithin cholesterol chelator = 72 25 3) were prepared by consecutive extrusion of lipid suspension in HEPES buffered saline, pH 7.4, through the set of polycarbonate filters with pore size of 0.6, 0.4, and 0.2 mm. Liposome final size was between 205 and 225 nm. Gd content determination was performed by Galbraith Laboratories, Inc. The relaxation parameters of all preparations were measured at room temperature using a 5-MHz RADX nuclear magnetic resonance proton spin analyzer. The relaxivity of liposomes with polymeric chelators is noticeably greater because of the larger number of Gd atoms bound to a single lipid residue [16].

A series of iomeprol-containing liposomes were evaluated in animals by Petersein et al. [62] and in healthy volunteers by Spinazzi et al. [63,64]. BR2 and BR21 are liposomes made of phosphatidyl choline (PC),dipalmitoyl phospatidic acid (DPPA) and cholesterol at a molar ratio of 2 1 (PC -i- DPPA/cholesterol) with an iodine content of 260 mg mL (BR2) and 320 mg mL" (BR21), respectively, and a size of 0.4 pm. BR2 contains 40 mg lipid mL and BR21 20 mg mL L In rabbits, BR2 tended to provide a higher and more persistent CT enhancement than BR21. 

We then examined the effect of phospholipid composition on the transfection activity. Liposomes containing various combinations of phospholipids were tested for transfection activity on BHK-21 and HeLa-S3 cells. As described in HVJ-AVE liposomes, the cationic liposomes containing all of ePC, DOPE, and eSph in equal molar amounts showed the highest transfection efficiency both with BHK-21 and HeLa-S3 cells. The same results were obtained with Ltk-, HEK 293, and NB-1 cells. We also examined other phospholipids, but none was observed to be more effective. We then examined the effect of the cholesterol/phospholipid ratio on the transfection efficiency. The phospholipid composition (ePC DOPE eSph = 1 1 1) and DC-Chol content (10% of total... 

Kirby, C., Clarke, J., and Gregoriadis, G. (1980), Cholesterol content of small unilamellar liposomes controls phospholipid loss to high density lipoproteins in the presence of serum, FEBS Lett., Ill, 324-328. 

Liposomes with compositions that imitate the skin s lipid content (ceramides, cholesterol, fatty acids, cholesterol sulfate) have also been prepared [37] and their pharmacological response on a skin barrier disruption model was assessed. Apart from their action as lipidic carriers for the repair of skin barrier, tliese liposomes are expected to penetrate easily the skin barrier due to their biocompatibilily with the stratum corneum. Many attempts have being made to incorporate ceramides, the major component of stratum corneum. These lipids have a relatively large stereochemical shape, and in the presence of water they tend to form multilamellar bilayers [50-53],... 

If the early endosomal release is not possible, another way to keep DNA intact in lysosome is to protect the DNA from lysosomal degradation. Cationic liposomes formulated with cholesterol believed to offer a useful role in keeping DNA intact (121,156,157). Straub-inger et al. (158) have demonstrated that the lysosomal enzymes work at lower pH, i.e., pH < 6. It was also shown that cholesterol-containing liposomes, which possess greater stability and lower ion-permeability compared with DOPE-containing liposomes, provide an improved stability to the lipid-DNA complex in the cytosol (158-160). It is easily conceivable that if the endosomal content passes onto lysosome before being released from endosomes, the lipid/DNA complex could remain secured in the lysosome. 

Gel to liquid-crystal melting transition for DPPC liposomes as a function of cholesterol content. Results are shown for aqueous liposomes (stars), liposomes freeze-dried without trehalose (triangles), and liposomes freeze-dried in the presence of trehalose (circles). 

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