Liposome lipid composition

The liposome lipid composition was varied in order to get (i) a high immunological response, (ii) to increase the dose, and (iii) to increase the stability of the formulation. A complete list of all investigated liposome formulations is given in Table 1. Liposomes were made with or without active ingredients. 

Active entrapment and loading stability are dependent on liposome lipid composition, lipid quality, medium composition, and temperature as well as on the pK and hydrophobicity of the base. The ammonium sulfate gradient approach differs from most other chemical approaches used for remote loading of liposomes, since it does not require liposomes with acidic pH interior or an alkaline extraliposomal phase. 

Liposomes Lipid compositions (% molar ratio) Muscle luciferase activity Livei luciferase activity ... 

Liposome Lipid composition (molar ratio) and surface modification linkage betweei PEG and liposome... 

Several studies have been performed in order to investigate the effect of liposomal size (Hirano and Hunt, 1985), lipid composition (Senior and Gregoriadis, 1982 Hirano et al., 1985), and lipid dose (Ellens et al., 1983, Kim et al., 1987) on the fate of liposomes after intraperitoneal administration. In the size range studied (0.048-0.72 Min), no size-dependent absorption could be expected (Hirano and Hunt, 1985). Particles larger than 22.5 pm are not expected to enter the lymphatic capillaries (Allen, 1956). After intraperitoneal administration of multivesicular liposomes (19 + 7 ym), Kim and Howell (1987a) and Kim et al. (1987) showed that liposomal entrapment of Ara-C prolongs the half-Ufe of the drug in the peritoneal... 

Barza, M., Stuart, M., and Szoka, F. (1987). Effect of size and lipid composition on the pharmacokinetics of intravitreal liposomes, Invest. Ophthalmol. Visual Sci., 28, 893-900. 

Crommelin, D. J. A. (1984). Influence of lipid composition and ionic strength on the physical stability of liposomes, J. Pharm. Sci.. 73, 1559-1563. 

A. (1990b). Effect of lipid composition on the in vivo integrity of doxorubicin-containing liposomes. Two pathways for sustained release of doxorubicin. Submitted. 

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... 

The half-life of liposomes administered in the blood stream is affected by the composition, size, charge, and fluidity. Liposomes with a small size or with a rigid lipid bilayer have a longer half-life (38 9). Large liposomes administered iv tend to accumulate at a lymph node near the injected site. This tendency can be useful for preventing metastases. Liposomes which pass through the lymph node have a tendency to accumulate in the RES, such as the liver and spleen (40,41). The disposition of liposomes is altered by the dose of liposomes as well as size or lipid composition of liposomes. Cholesterol rich liposomes are cleared slower due to... 

Many types of liposomes of different lipid composition and different sizes having a transmembrane AS gradient were prepared (10). These liposomes varied (i) in their liposome-forming phosphatidylcholine (PC), being with and without cholesterol and/or lipopolymer (ii) in their size and (iii) in their method of preparation. The approaches for preparing these different liposome formulations varies in their lipid hydration and downsizing. Table 1 in Haran et al. (10) gives a partial list of such liposome preparations. In all cases the scheme of liposome preparation can be summarized as described in Table 4. 

Mayer LD, Tai LC, Ko DS, et al. Influence of vesicle size, lipid composition, and drug-to-lipid ratio on the biological activity of liposomal doxorubicin in mice. Cancer Res 1989 49 5922. 

Kirby C, Gregoriadis G. The effect of lipid composition of small unilamellar liposomes containing melphalan and vincristine on drug clearance after injection into mice. Biochem Pharmacol 1983 32(4) 609. 

Table 1 Lipid Composition of All Liposomal Formulations Mentioned in the Text...

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. 

For water-soluble agents, the encapsulation efficiency and thus the internal volume of vesicles which determines the amount of encapsulated material, is a very important factor with regard to the in vitro efficacy. It depends on the liposome size, lipid composition and lamellarity. When the number of liposomes delivered has to be known, the enumeration of the suspension can be performed by multinuclear NMR and photon correlation spectroscopy (110)-... 

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