Liposomes basic

Liposomes are members of a family of vesicular structures which can vary widely in their physicochemical properties. Basically, a liposome is built of one or more lipid bilayers surrounding an aqueous core. The backbone of the bilayer consists of phospholipids the major phospholipid is usually phosphatidylcholine (PC), a neutral lipid. Size, number of bilayers, bilayer charge, and bilayer rigidity are critical parameters controlling the fate of liposomes in vitro and in vivo. Dependent on the preparation procedure unilamellar or multilamellar vesicles can be produced. The diameter of these vesicles can range from 25 nm up to 50 ym—a 2000-fold size difference. 

Thus, liposomes—with or without adjuvants—have a potential as antigen delivery systems. No clear insights exist on how to prepare liposome-based vaccines with optimum immunological properties by rationale instead of by trial and error. Therefore, much basic work is needed to unravel the mechanisms involved. 

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]. 

QSAR studies of the pH-dependent partitioning of acidic and basic drugs into liposomes [64] yielded following equations ... 

Schaper, K.-J., Zhang, H., Raevsky, 0. A. pH-dependent partitioning of acidic and basic drugs into liposomes - a quantitative structure-activity relationship. Quant. Struct.-Act. Relat. 2001, 20, 45-54. 

Austin et al. [132] measured the ionic strength dependence of the liposome-water distribution of several acidic and basic drugs and modelled the data with a combination of electrostatic and ion pair models. They concluded that the increased apparent Dmw values at higher ionic strength were due primarily to the reduction in surface potential and not to ion pairing. Ion pairing was also excluded because the apparent Dmw varied at fixed ionic strength with the... 

Gabizon A, Goren D, Cohen R, Barenholz Y (1998) Development of liposomal anthracyclines from basics to clinical applications. Journal of Controlled Release 53 275-279. 

Gabizon A, Barenholz Y. Liposomal anthracyclines— from basics to clinical approval of PEGylated liposomal doxorubicin. In Janoff AS, ed. Liposomes Rational Design. New York Marcel Dekker, 1999 343-362. 

Barenholz Y. Design of liposome-based drug carriers from basic research to application as approved drugs. In Lasic DD, Papahadjopoulos D, eds. Medical Applications of Liposomes. Amsterdam Elsevier Science, 1998 541-565. 

Fenske DB, Maurer N, Cullis PR. Encapsulation of weakly-basic drugs, anti-sense oligonucleotides and plasmid DNA within large unilamellar vesicles for drug delivery applications. In Torchilin VP, Weissig V, eds. Liposomes A Practical Approach. 2nd ed. Oxford Oxford University Press, 2002, Chapter 6. 

Schuber F. Chemistry of ligand-coupling to liposomes. In Philippot JR, Schuber F, eds. Liposomes as Tools in Basic Research and Industry. Boca Raton CRC Press, 1995 21. 

The basic principle is shared by several methods In chromatographic or electrophoretic systems where the liposomes (vesicles) are immobilized, pseudostationary, or carried by an electroendosmotic flow, migrating amphiphilic drug molecules partition between the water outside the liposomes, the lipid bilayer of the liposome, and the aqueous compartment within the liposome (Fig. 3). In all cases the migration rate basically reflects the par-... 

Another example of ACE analyses of solute-bilayer interactions was described by Roberts et al. (50), who observed retardation of riboflavin by liposomes. Analyses technically similar to liposomal ACE have been performed with mixed bile salt/phosphatidylcholine/fatty acid micelles (95). The partitioning of basic and acidic drugs depended on the acid-base properties of the drug and on the shape and charge of the mixed micelles. 

Much research has gone into raising the sensitivity and selectivity of immunosensors to the desired levels. Several labels have proved to ensure a high sensitivity, yet radioisotopic labels have essentially been avoided. Non-isotopic labels for immunosensors include various enzymes, catalysts, fluorophores, electrochemically active molecules and liposomes. Labelled immunosensors are basically designed so that immunochemical complexation takes place on the surface of the sensor matrix. There are several variants of the procedure used to form an immunocomplex on the matrix. In the final step, however, the label should always be incorporated into the immunocomplex for determination, as shown in Fig. 3.27.B. 

New RRC. Influence of liposome characteristics on their properties and fate. In Phihppot JR, Schuber F, editors. Liposomes as tools in basic research and industry. Boca Raton (EL) CRC Press 1995. pp. 3-20. 

Perhaps one of the very first examples of enzymatic reactions carried out in liposomes with the aim of building a minimal cell is the work by Schmidli et al. (1991), as already mentioned in the previous chapter (Fig. 10.5). The general idea is illustrated in Figure 11.6, whereas the biochemical pathway is illustrated in Figure 11.7. The basic idea is to have inside the liposomes the series of reactions that, starting from a relatively simple product (G3P, glycerol-3-phosphate)... 

Many other delivery systems have been employed in attempts to improve the delivery of anticancer drugs. The major types include liposomes, microspheres, nanoparticles and immunotoxins. This review concentrates on soluble polymeric carriers. However, basic characteristics of alternate delivery systems have been included to permit the reader the comparison of different delivery systems. 

Immordino ML, Dosio F et al (2006) Stealth liposomes Review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine 1(3) 297-315... 

There is a wide variety of vectors used to deliver DNA or oligonucleotides into mammalian cells, either in vitro or in vivo. The most common vector systems are based on viral [retroviruses (9, 10), adeno-associated virus (AAV) (11), adenovirus (12, 13), herpes simplex virus (HSV) (14)] andnonviral [cationic liposomes (15,16), polymers and receptor-mediated polylysine-DNA] complexes (17). Other viral vectors that are currently under development are based on lentiviruses (18), human cytomegalovirus (CMV) (19), Epstein-Barr virus (EBV) (20), poxviruses (21), negative-strand RNA viruses (influenza virus), alphaviruses and herpesvirus saimiri (22). Also a hybrid adenoviral/retroviral vector has successfully been used for in vivo gene transduction (23). A simplified schematic representation of basic human gene therapy methods is described in Figure 13.1. 

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