On liposomes

Prolonged presence of the drug at the site of injection is the aim of liposome encapsulation of drugs, which are injected in the vitreous body. Both amphotericin and gentamicin in liposome formulations were cleared from the injection site significantly more slowly than the free drug residence times depended on liposome size and, in some cases, on bilayer composition (Tremblay et al., 1985 Barza et al., 1985, 1987 Fishman et al., 1986). 

The effects of liposome size and surface charge on liposome-mediated delivery of methotrexate-gamma-aspartate to cells in vitro, Biochim. Biophys. Acta, 820, 74-84. 

A. (1986a). Preparation of liposomes via detergent removal from mixed micelles by dilution. The effect of bilayer composition and process parameters on liposome characteristics, Pharm. Weekbl. 

Kunimoto, M., Inoue, E., and Nojima, S. (1981). Effect of ferrous ion and ascorbated induced lipid peroxidation on liposomal membranes, Biochim. Biophys. Acta, 646, 169-178. 

In this chapter we describe the basic principles involved in the controlled production and modification of two-dimensional protein crystals. These are synthesized in nature as the outermost cell surface layer (S-layer) of prokaryotic organisms and have been successfully applied as basic building blocks in a biomolecular construction kit. Most importantly, the constituent subunits of the S-layer lattices have the capability to recrystallize into iso-porous closed monolayers in suspension, at liquid-surface interfaces, on lipid films, on liposomes, and on solid supports (e.g., silicon wafers, metals, and polymers). The self-assembled monomolecular lattices have been utilized for the immobilization of functional biomolecules in an ordered fashion and for their controlled confinement in defined areas of nanometer dimension. Thus, S-layers fulfill key requirements for the development of new supramolecular materials and enable the design of a broad spectrum of nanoscale devices, as required in molecular nanotechnology, nanobiotechnology, and biomimetics [1-3]. 

The second model of a biological membrane is the liposome (lipid vesicle), formed by dispersing a lipid in an aqueous solution by sonication. In this way, small liposomes with a single BLM are formed (Fig. 6.11), with a diameter of about 50 nm. Electrochemical measurements cannot be carried out directly on liposomes because of their small dimensions. After addition of a lipid-soluble ion (such as the tetraphenylphosphonium ion) to the bathing solution, however, its distribution between this solution and the liposome is measured, yielding the membrane potential according to Eq. 

The most versatile method to prepare such hollow capsules is self-assembly [203-205, 214, 215]. Owing to their amphiphilic nature and molecular geometry, lipid-based amphiphiles can aggregate into spherical closed bilayer structures in water so-called liposomes. It is quite reasonable that the hollow sphere structure of liposomes makes them suitable as precursors for the preparation of more functional capsules via modification of the surfaces with polymers and ligand molecules [205, 216, 217]. Indeed, numerous studies based on liposomes in this context have been performed [205, 209, 213]. 

Tetraethyllead was used in the past as an antiknock agent in gasoline, but it has been phased out in most countries. Alkyllead compounds have a detergent-like activity on liposomes and black lipid membranes [232], Tributyllead destroys planar lipid membranes at lower concentrations than tripropyllead, which is again more effective than triethyl- and trimethyllead [232]. Inorganic lead compounds like lead acetate and lead nitrate were effective only at twice as high concentrations [232]. 

Horowitz AT, Barenholz Y, Gabizon AA. In vitro cytotoxicity of liposome-encapsulated doxorubicin dependence on liposome composition and drug release. Biochim Biophys Acta 1992 1109 203-209. 

Monkkonen J, Liukkonen J, Taskinen M, Heath TD, Urtti A. Studies on liposome formulations for intraarticular delivery of clodronate. J Control Release 1995 35 145-154. 

Carrion C, Domingo JC, de Madariaga MA. Preparation of long-circulating immunoliposomes using PEG-cholesterol conjugates effect of the spacer arm between PEG and cholesterol on liposomal characteristics. Chem Phys Lipids 2001 113 97. 

Integrin receptor-binding peptides have been used to enhance liposome binding, uptake, and expression (25,47 9). The inclusion of an 0(5pi integrin-targeted peptide into a liposomal complex enhanced transfection efficiency four- to five-fold in Jurkat cells and 10- to 13-fold in TF-1 cells (48). Confocal and electron microscopy revealed that the mechanism of cell entry conferred by RGD peptides on liposomes is predominantly by clathrin-coated endocytosis rather than by phagocytosis (50). 

Poulain FR, Allen L, Williams MC, et al. Effects of surfactant apolipoproteins on liposome structure implications for tubular myelin formation. Am J Physiol 1992 262(6 Pt 1) L730-L739. 

Block dynamin dependent processes dynamin is not only involved in clathrin uptake (see section Dynamin Dependence on Liposome Uptake )... 

The calcineurin inhibitors tacrolimus (FK 506) and cyclosporin A block the function of dynamin and are thought to be specific for clathrin-mediated uptake (50). The smal guanosine triphosphate (GTP)ase dynamin is also involved in other processes and is therefore described in section Dynamin Dependence on Liposome Uptake. ... 

Because of the strict requirement for actin, the most commonly used inhibitors of macropinocytosis are the cytochalasins, especially cytochalasin D or toxin C. These substances also block phagocytosis and intracellular trafficking along actin filaments. Therefore, the results from these experiments are described in the trafficking section Actin Dependence on Liposome Uptake. ... 

Energy Dependence on Liposome Uptake and Fusion with Cell Membranes... 

Incubation at 4°C (see section Energy Dependence on Liposome Uptake and Fusion with Cell Membranes ) and a block of metabolic activity (see section Metabolic Activity ) might also be used to block endocytosis and to detect cellular association or fusion. 

SK Wiedmer, J Hautala, JM Holopainen, PKJ Kinnunen, M-L Riekkola. Study on liposomes by capillary electrophoresis. Electrophoresis 22 1305-1313... 

Fig. 8 Capillary EKC separations of (A) acetophenone (1), propiophenone (2), butyrophenone (3), valerophenone (4), and hexanophenone (5) on vesicles composed of sodium dodecylsulfate and ra-dodecyltrimethylammoniumbromide at pH 7.2, (B,C) of 1-dehydroaldosterone (1), cortisone (2), cortisol (3), 21-deoxycortisol (4), 11-deoxycortisol (5), and dexamethasone (6) on liposomes composed of 1-palmitoyl-2-oleoyl-sra-glycero-3-phosphocholine (80%) and (B) phosphatidylserine or (C) car-diolipin at pH 9, lipid concentrations (B) 2.4 mM and 0.6 mM, (C) 3.6 and 0.9 mM. (Part A is reprinted with permission from Ref. 59, copyright 1998 American Chemical Society Parts B and C are reprinted with permission from Ref. 33, copyright 2000 Wiley-VCH Verlag, all with slight modifications.)...

Fluorescence probing has also been used by us to investigate the mechanism of vesicle to micelle transformation due to interaction of liposome with sodium dodecyl sulfate micelles. An increase in optical density and hydrodynamic diameter was observed at low SDS concentrations (Fig. 24). The increase was attributed to the incorporation of SDS monomers on liposome vesicles. The point where the hydrodynamic diameter and optical density reached a maximum was proposed to correspond to the saturation of bilayers of the first inflection point. Upon further increase in the SDS concentration... 

Domain Effect on Liposome Membrane Functional Attribute on Lipid BUayer... 

Ogawa, Y, H. Kawahara, N. Yagi, M. Kodaka, T. Tomohiro, T. Okada, T. Konakahara, and H. Okuno, Synthesis of a novel lipopeptide with alpha-melanocyte-stimulating hormone peptide ligand and its effect on liposome stability [published erratum appears in Lipids, 1999 34(6) 643]. Lipids, 1999. 34(4) 387-94. 

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