Unilamellar liposome

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. 

Freeze-thawing If SUV are freeze-thawed in the presence of a high concentration of electrolytes and subsequently dialyzed against a low electrolyte concentration, unilamellar liposomes with a diameter of more than 10 pm are formed. The formation of these giant... 

Allen, T. M., and Chonn, A. (1987). Large unilamellar liposomes with low uptake into the reticuloendothelial system, FEBS Lett., 223. 42-46. 

Ellens, H., Morselt, H. W. M., Dontje, B. H. J., Kalicharan, D., Hulstaert, C. E., and Scherphof, G. L. (1983). Effects of liposome dose and the presence of lymphosarcoma cells on blood clearance and tissue distribution of large unilamellar liposomes in mice, Cancer Res.. 43. 2927-2934. 

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. 

Spherical unilamellar liposomes [119] Planar phospholipid bilayer [141,142]... 

EGC > EC = C determined using artificial water-soluble phenothiazine radical cations (Salah et al., 1995) and EGCG > EGC > ECG > C determined in a mixture of LDL and VLDL. However, in the oxidation of unilamellar liposomes of phosphatidylcholine initiated with a water-soluble azo compound at 37°C, the antioxidant activities of EGCG and EGC were lower than those of EC and ECG at pH 7.4, and their depletion of EGCG and EGC was faster than that of EC and ECG (Terao et al, 1994). 

Chen G and Djuric Z. 2001. Carotenoids are degraded by free radicals but do not affect lipid peroxidation in unilamellar liposomes under different oxygen tensions. FEBS Letters 505(1) 151-154. colorMaker, Inc. Anaheim, CA, http //www.colormaker.com/CM/AboutNC/annatto.asp. 

Cantrell et al. (2003) studied the quenching of 02 by several dietary carotenoids in dipalmitoyl phosphatidylcholine (DPPC) unilamellar liposomes. These workers used water soluble and lipid soluble 02 sensitizers so that a comparison of the efficiencies of quenching 02 generated within and outside the membrane model could be made. Perhaps surprisingly there was little difference in the efficiency of quenching in either situation. Typical results are presented in Table 14.3 (taken from Cantrell et al. (2003 and 2006)). 

FIGURE 14.4 Rate of decay of 02 against (3-CRYP concentration in air-saturated solutions of DPPC unilamellar liposomes using either RB or PBA as ()2 sensitizer. 

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. 

Kim, S., and Martin, G.M. (1981) Preparation of cell-size unilamellar liposomes with high captured volume and defined size distribution. Biochim. Biophys. Acta 646, 1-9. 

Szoka, F., Olson, F., Heath, T., Vail, W., Mayhew, E., and Paphadjopoulos, D. (1980) Preparation of unilamellar liposomes of intermediate size (0.1-0.2 pm) by a combination of reverse phase evaporation and extrusion through polycarbonate membranes. Biocbim. Biophys. Acta 601, 559-571. 

Shek, P.N., B.Y.K. Yung, N.Z. Stanacev, Comparison between Multilamellar and Unilamellar Liposomes in Enhancing Antibody Formation, Immunology. 49, 37,1983. 

Nichols, J. W. and Deamer, D. W. (1980). Net proton hydroxyl permeability of large unilamellar liposomes measured by an acid-base titration technique, Proc. Natl Acad. Sci. USA, 77, 2038-2042. 

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

Dithiocarbamates and xanthates form particularly stable, neutral complexes with Cu(II), Cd(II) (and also Ni, Hg, Pb), which are membrane permeable and increase the apparent bioaccumulation of these metals [13]. In the series of sulfoxine, oxine, and chloroxine, the hydrophobicity of the neutral and the charged form, as well as of the Cu complex, increases. While the sulfoxine is not hydrophobic and does not modulate copper toxicity [220], the Cu-oxine complex is hydrophobic with an octanol-water partition constant, log Kok, of 1.7 [221] or 2.6 [222]. Chloroxine can be assumed to be even more hydrophobic, but so far its influence on uptake and toxicity has not been investigated. Uptake of Cu2+ into unilamellar liposomes was increased in the presence of 8-hydroxy-chinoline, and decreased again after adding HA [223],... 

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). 

Lin HY, Thomas JL. Factors affecting responsivity of unilamellar liposomes to 20 kHz ultrasound. Langmuir 2004 20 6100-6106. 

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... 

Rubas W, et al. Treatment of murine L1210 leukemia and melanoma B16 with lipophilic cytosine arabinoside prodrugs incorporated into unilamellar liposomes. Int J Cancer 1986 37 149. 

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. 

Alder-Moore JP, Proffitt R. Development, characterisation, efficacy and mode of action of AmBisome, a unilamellar liposomal formulation. J Liposome Res... 

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.

The encapsulation of pDNA can also be accomplished with the use of a detergent dialysis procedure (12). In contrast to the PFV approach, the detergent dialysis procedure starts off with a micellar system and leads to encapsulation of pDNA in unilamellar liposomes called SPLP after detergent removal. Plasmid entrapment relies on a delicate balance between cationic lipid content and ionic strength of the solution. 

Morphology. Structural details were visualized by cryo-TEM. Figure 1A is a cryo-TEM image of a sample with an entrapped oligonucleotide-to-lipid ratio of 0.13 mg/mg. It confirms the coexistence of unilamellar liposomes with bi- and multilamellar liposomes. The membranes of the latter are in close contact. The inset of Figure 1A is an expanded view of a multilamellar... 

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. 

Unilamellar liposomes are nanoparticles made of a bilayer, most often phospholipidic, entrapping an internal aqueous core. Formed spontaneously in the presence of an excess of water and above the gel-to-liquid crystal phase tran-... 

---