Biological liposomes

Several mechanisms between drug-encapsulated liposomes and cells was presented [9,10]. Sunamoto and coworkers [11] applied the liposomal technique for improving the biological activity of polyanionic polymers. 

They encapsulated poly(MA-CDA) into mannan-coated liposomes and evaluated superoxide production from mouse macrophages. The activity was three- to five-fold high compared with uncapsulated poly(MA-CDA) itself [5,11], suggesting that an increased incorporation of the polymer by the receptor-mediated endocytosis mediated the higher biological activity.. 

T. Espevik, M. Otterlei, G. Skjak-Braek, L. Ryan, S. D. Wright, and A. Sundan, Eur. J. Immunol. 23 255 (1993). P. Machy and L. Leserman, Liposomes in Cell Biology and Pharmacology, John Libbey Eurotext, London and Paris (1987). 

Phospholipids e.g. form spontaneously multilamellar concentric bilayer vesicles73 > if they are suspended e.g. by a mixer in an excess of aqueous solution. In the multilamellar vesicles lipid bilayers are separated by layers of the aqueous medium 74-78) which are involved in stabilizing the liposomes. By sonification they are dispersed to unilamellar liposomes with an outer diameter of 250-300 A and an internal one of 150-200 A. Therefore the aqueous phase within the liposome is separated by a bimolecular lipid layer with a thickness of 50 A. Liposomes are used as models for biological membranes and as drug carriers. 

Dorn, K., Hupfer, B., and Ringsdorf, H. Polymeric Monolayers and Liposomes as Models for Biomembranes How to Bridge the Gap Between Polymer Science and Membrame Biology Vol. 64, pp. 1 —54. 

Phospholipids are a major component of all biological membranes together with glycolipids and cholesterol. Due to their polar nature, i.e. hydrophilic head and hydrophobic tail, phospholipids form in water vesicles or liposomes. 

Gregoriadis, G. (1980). Recent progress in liposome research, in Liposomes in Biological Systems (G. Gregoriadis and A. C. 

Lichtenberg, D., and Barenholz, Y. (1988). Liposomes Preparation, characterization and preservation, in Methods of Biological Analysis. Vol. 33 (D Glick, ed.), John Wiley and Sons, New York, pp. 337-461. 

Machy, P., and Leserman, L. (eds.) (1987). Liposomes in Cell Biology and Pharmacology, John Libbey Eurotext Ltd/INSERM, Great Britain. 

Yau-Yong, A., Chow, J., and Law, M. (1986). Liposome delivery of a biologically active peptide, 133rd Ann. Meeting Am. Pharm Assoc.. 16, 105. 

Today, lipophilicity can be determined in many systems that are classified by the characteristics of the nonaqueous phase. When the second phase is an organic solvent (e.g. n-octanol), the system is isotropic, when the second phase is a suspension (e.g. liposomes), it is anisotropic, and when the second phase is a stationary phase in liquid chromatography, it is an anisotropic chromatographic system [6]. Here, we discuss the main aspects of isotropic and anisotropic lipophilicity and their biological relevance the chromatographic approaches are investigated in the following chapter by Martel et al. 

Whereas the relationship of solute permeability with lipophilicity has been studied in a large number of in vivo systems (including intestinal absorption models [54,55], blood-brain [56 58] and blood nerve [59] barrier models, and cell culture models [60 62], to name just a few), numerous in vitro model systems have been developed to overcome the complexity of working with biological membranes [63-66]. Apart from oil-water systems that are discussed here, the distribution of a solute between a water phase and liposomes is... 

A challenge in designing liposome systems is the assessment of drug release from such systems in vitro. Use of agarose gel matrices has been reported as one approach to evaluate the release kinetics of liposome-encapsulated materials in the presence of biological components [68],... 

The important attributes of liposomes as a drug carrier are (a) they are biologically inert and completely biodegradable (b) they pose no concerns of toxicity, antigenicity, or pyrogenicity, because phospholipids are natural components of all cell membranes (c) they can be prepared in various sizes, compositions, surface charges, and so forth, depending on the requirements of... 

G. Poste, R. Kirsh, and T. Koestler, eds. Liposome Technology. Targeted Drug Delivery and Biological Interactions, Vol. 3, CRC Press, Boca Raton, FL, 1984. 

The octanol-water partition model has several limitations notably, it is not very biological. The alternative use of liposomes (which are vesicles with walls made of a phospholipid bilayer) has become more widespread [149,162,275, 380—4441. Also, liposomes contain the main ingredients found in all biological membranes. 

There are no convenient databases for liposome log P values. Most measured quantities need to be ferreted from original publications [149,162,376,381-387,443], The handbook edited by Cevc [380] is a comprehensive collection of properties of phospholipids, including extensive compilations of structural data from X-ray crystallographic studies. Lipid-type distributions in various biological membranes have been reported [380,388,433]. 

Rogers, J. A. Choi, Y. W., The liposome partitioning system for correlating biological activities for imidazolidine derivatives, Pharm. Res. 10, 913-917 (1993). 

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. 

Papahadjopoulos, D. (Ed.), Liposomes and Their Use in Biology and Medicine, Annals of the New York Academy of Science, Vol. 308, New York, 1978. 

Wilschiit, J., and D. Hoekstra, Membrane fusion from liposomes to biological membranes, Trends Biochem. Sci., 9, 479 (1984). 

New developments in immobilization surfaces have lead to the use of SPR biosensors to monitor protein interactions with lipid surfaces and membrane-associated proteins. Commercially available (BIACORE) hydrophobic and lipophilic sensor surfaces have been designed to create stable membrane surfaces. It has been shown that the hydrophobic sensor surface can be used to form a lipid monolayer (Evans and MacKenzie, 1999). This monolayer surface can be used to monitor protein-lipid interactions. For example, a biosensor was used to examine binding of Src homology 2 domain to phosphoinositides within phospholipid bilayers (Surdo et al., 1999). In addition, a lipophilic sensor surface can be used to capture liposomes and form a lipid bilayer resembling a biological membrane. 

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