Small unilamellar liposomes

Senior, J., and Gregoriadis, G. (1982). Stability of small unilamellar liposomes in serum and clearance from the circulation The effect of the phospholipid and cholesterol components. Life Sci., 30. 2123-2136. 

Gregoriadis, G., and Senior J. (1980) The phospholipid component of small unilamellar liposomes controls the rate of clearance of entrapped solutes from the circulation. FEBS Lett. 119, 43—46. 

SUV = small unilamellar liposomes, LUV = large unilamellar liposomes. 

Liposome Formation. The pioneering investigations of Bang-ham (5) have shown that thin films of natural phospholipids form bilayer assemblies if they are lyophilized in excess water by simple handshaking above the phase transition temperature. While this procedure results in the formation of large, multibilayered spherical structures, by ultrasonication of such lipid dispersions small unilamellar liposomes are formed (16), which are schematically shown in Figure 10. Additional metTiods for liposome preparation are described in a number of reviews (17,44,45,46). 

Incorporation of Lipophilic Antitumor and Antiviral Drugs into the Lipid Bilayer of Small Unilamellar Liposomes... 

Since the discovery of vesicular structures, termed liposomes, by Alec Bangham, a tremendous amount of work on applications of liposomes has emerged. The use of small unilamellar liposomes as carriers of drugs for therapeutic applications has become one of the major fields in liposome research. The majority of these applications are based on the encapsulation of water-soluble molecules within the trapped volume of the liposomes. Long circulating poly(ethylene glycol) (PEG) modified liposomes with cytotoxic drugs doxorubicin, paclitaxel, vincristine, and lurtotecan are examples of clinically applied chemotherapeutic liposome formulations (1,2). 

Preparation of Small Unilamellar Liposomes Containing ara-C-NOAC, 5-Fdu-ara-C-NOAC, and NOAC-ETC... 

In one experiment, LC-AmB was compared with AmBisome (small unilamellar liposomes). LC-AmB was found to have an ED50 of 0.19 mg/kg and an ED90 of 0.51 mg/kg, whereas for AmBisome both these parameters were below 0.20 mg/kg, the lowest dose tested. In another experiment, LC-AmB was compared with Abelcet and showed a better reduction of parasite burden after three injections of 1 mg/kg, but there were not sufficient data to allow ED50 values to be calculated (22). Therefore, we can conclude that this new AmB formulation retains antileishmanial activity in vivo, but it is difficult to position it with respect to other formulations. 

Figure 3 Design of a diepitope liposomal construct. Small unilamellar liposomes (PC/PG/Chol 55/25/50 molar ratio diameter 100nm) containing 10mol% of bromo-acetyl l,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine and 10mol% of the thiol-reactive lipopeptide adjuvant anchor Pam3CysAlaGly-Mal were reacted, at 25°C successively at pH 6.5, with the T-helper epitope QYI, derivatized with a C-linker at its N-terminus, followed at pH 9.0 by the B-epitope TPE derivatized with a CG linker at its N-terminus. Abbreviations PC, phosphatidylcholine PE, phosphatidylethanolamine SUV, small unilamellar vesicles. Source From Refs. 11, 20, 21.

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. 

Schwendener, R. A., Wuethrich, R., Duewell, S., Westera, G., and Von-Schulthess, G. K. Small unilamellar liposomes as magnetic resonance contrast agents loaded with paramagnetic manganese-, gadolinium-, and iron-DTPA-stearate complexes. Int. J. Pharm. 1989, 49, 249-259. 

The ACE analysis of interactions between drugs and phospholipid bilayers of liposomes present as a pseudostationary phase was performed by Zhang et al. (32). The capillaries were treated to eliminate electroendosmosis. Freshly prepared and essentially neutral small unilamellar liposomes composed of egg phosphatidylcholine were sucked into the capillary. These liposomes increased both the retention of four negatively charged drugs and the separation between the substances (Fig. 6). The chromatographic retentions of these drugs on immobilized phosphatidylcholine liposomes, ex-... 

Figure 14.2 Illustration of a large multilamellar liposome (top) and a small unilamellar liposome (bottom). In each case lipid bilayers are the structural units (inset). From Yang and Alexandridis [890]. Copyright 2000, Elsevier.

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 have received considerable attention as a possible delivery tool for peptide and protein drugs by protecting labile compounds from degradation or by enhancing the uptake of poorly absorbed compounds. Liposomes have been studied extensively as a potential oral delivery system for proteins, especially insulin, and the oral administration of liposome-entrapped insulin into diabetic rats has produced a significant fall in blood glucose levels. " There are three types of liposomes multilamellar liposomes (MLV), 0.05-10 pm small unilamellar liposomes (SUV),... 

Longuet P, Joly V, Amirault P, et ai. Limited protection by small unilamellar liposomes against the renal tubular toxicity induced by repeated amphotericin B infusions in rats. Antimicrob Agents Chemother 1991 35 1303-8. 

Here, we present methods of preparation of liposomal vaccines and results obtained in our laboratories with small unilamellar liposomes as carriers of antigen peptides and peptide encoding DNA plasmids, demonstrating their high potential as therapeutic vaccine formulations against infectious diseases and cancers. 

Figure 19.2. (a) Small unilamellar liposome (SUV, 20-50 nm). (b) Multilamellar vesicles (MLV, up to 10 um), (c) Large unilamellar vesicle (LUV, 50 nm-10 um). (d) A liposome can encapsulate water-soluble drugs inside the cavity and nonpolar molecules within the... 

Gregoriadis G, Meehan A, Mah MM. Interaction of antibody-bearing small unilamellar liposomes with target free antigen in vitro and in vivo—some influencing factors. Biochem J 1981 200 203-210. 

Chow, D. D., Essien, H. E., Padki, M. M., and Hwary, K. J. (1989) Targeting small unilamellar liposomes to hepatic parenchymal cells by dose effect. J. Pharmacol. Exp. Ther. 248, 506-513. 

A number of studies have also attempted to measure the transmembrane movement, or flip-flop , of cholesterol. Poznansky and Lange [142] and Lenard and Rothman [143] have shown that in sonicated dipalmitoylglycerophospho-choline-cholesterol liposomes and in influenza virus membranes, respectively, the half-time for flip-flop of cholesterol was in excess of 6 days, if it occurred at all. However, other workers have reported rapid transmembrane and intermembrane movement of cholesterol in small unilamellar liposomes [144-147]. 

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