Leakage from Liposomes

Aggregation of liposomes upon storage also depends on membrane components. Liposomes that included taurine as an isotonic solute were most stable at an optimal content of benzalkonium chloride.721 Repulsive energy forces between particles described by the Deryaguin-Verwey-Overbeek theory appeared to account for the stabilization. 

Liposome composition11 Room temperature Room temperature, oxygen-free 4°C 

Abbreviations EYL, egg yolk lecithin Choi, cholesterol a-T, a-tocopherol. 

Functional Changes in Dosage Forms with Time 

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Hays LM, et al. Antifreeze glycoproteins inhibit leakage from liposomes during thermotropic phase transitions. Proc Natl Acad Sci USA 1996 93 6835-6840. 

Figure 182. 5(6)-Carboxyfluorescein leakage from liposomes during incubation at 20°C for 70 h in collagen-containing solutions as a function of collagen concentration. Lipid concentration O, 0,0.04% B, 0.4%. (Reproduced from Ref. 720 with permission.)...

Steroids These compounds are highly often present in lichens. Steroids have been reported to have antibacterial properties the correlation between membrane lipids and sensitivity for steroidal compound indicates the mechanism in which steroids specifically associate with the membrane lipid and exert its action by causing leakages from liposomes (Epand et al. 2007 Mohanuned 2013). 

INCREASED LEAKAGE FROM AGEING POLLEN COINCIDES WITH INCREASED LEAKAGE FROM LIPOSOMES PRODUCED FROM ITS PURIFIED LIPIDS... 

Liposomes The pH-sensitive liposomes so developed were able 56 to overcome the three main problems associated with liposomes, i.e., low stability, slow drug release and accumulation In liver/spleen. The ECM targeting liposome could prevent protein adsorption and drug leakage from liposome due to the biotin 2-PEG cross-linker located on interface of liposome. The uptake within the cancer cell is improved and could actively target tumor in tumor ECM to increase tumor accumulation. Also the drug release was enhanced at low pH, thus the potential bioavailability and drug resistance problem are also avoided. 

An alternative approach to avoid drug leakage from the liposomes on storage is to minimize the volume of the external water phase by... 

Steel CC, Drysdale RB (1988) Electrolyte leakage from plant and fungal tissues and dismption of liposome membranes by a-tomatine. Phytochemistry 27 1025... 

In vitro studies by Roddick and Drysdale on the effect of tomatine on the leakage of peroxidases from liposomes also support the idea that tomatine binds membrane sterols. They detected a significant disruption of the liposome by tomatine, only if the membranes contained sterol and additionally this destabilization was pH-dependent [27]. Later it was demonstrated that liposome membranes containing sterols but lacking 30-hydroxy sterol were resistant to tomatine [28]. 

Kristiansen, J. (1992), Leakage of a trapped fluorescent marker from liposomes Effects of eutectic crystallization of NaCl and internal freezing, Cryobiology, 29, 575-584. 

Copeland, E.S., Alving, C.R., and Grenan, M.M. (1976) Light-induced leakage of spin label marker from liposomes in the presence of phototoxic phenothiazines, Photochem. Photobiol., 24, 41-48. 

Wymer, N.J., Gerasimov, O.V., and Thompson, D.H. (1998) Cascade liposomal triggering light-induced Ca2+ release from diplasmenylcholine liposomes triggers PLA2-cata-lyzed hydrolysis and contents leakage from DPPC liposomes, Bioconjugate Chem., 9, 305-308. 

Figure 181. Effect of membrane components on the leakage of 5-fluorouracil from liposomes during storage at 4°C. O, LW (PC/PS/CH 7 4 5) A, LUV (MC/PS/CH 7 4 5) O, MLV (PC/PS/CH 7 4 5). LW, Large unilamellar vesicle, PC, l,2-dipalmitoyl-sn-glycero-3-phosphocholine monohydrate, PS, dipalmitoyl-DL-C phosphatidyl-L-serine, CH, cholesterol, MC, l,2-dimyristoyl-sn-glycero-3-phosphocholine monohydrate, MLV, multilamellar vesicle. (Reproduced from Ref. 717 with permission.)...

Parenteral, especially intravenous, administration of dmgs encapsulated in liposomes requires control of the pharmacokinetics of the dmg and this necessitates control of (1) concentration of the free dmg in the blood. (2) Concentration of liposomes and their entrapped dmg in blood. (3) Leakage rate of dmg from liposome in the blood. (4) The disposition of the intact dmg-carrying liposomes in the blood. 

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