Physical stability of different liposome compositions obtained by extrusion method.
Six different liposome compositions were evaluated according their physical stability. The compositions used were (in mole ratio): dipalmitoylphosphatidylcholine (DPPC): DPPC:cholesterol (CHOL) (1:1), DPPC:CHOL (1:6:1), DPPC:CHOL:sphingomyelin (SFM) (7:2:1), DPPC:CHOL:stearylamine (STE) (8:5:1) and DPPC:CHOL:dicetyl phosphate (DCP) (8:5:1). The liposomes were obtained by the extrusion method, through polycarbonate membranes of 0.1 micron pore size. The captured volume, number of lamellae, size and polydispersity of the vesicle populations were determined for all compositions. The physical stability was checked at -20 degrees C, room temperature, 4 degrees C and 50 degrees C by determining the changes in vesicle size over a maximum of 40 days. The process of aggregation and/or fusion was observed by photon correlation spectroscopy. From the results, we can establish that the above compositions are metastable at a temperature of 50 degrees C. On the other hand, values of captured volume were smaller than predicted by theory. This fact can be explained by the non-sphericity of extruded vesicles. In relation to the stability, the introduction of CHOL in the formulation allows keeping the vesicles at 4 degrees C. In contrast, liposomes containing only DPPC are very stable at room temperature. Compositions with a high stability are those that have present SFM or STE. The latter keeps the structural bilayer at temperatures < 0 degrees C without cryoprotectors. Both the lipids, STE and DCP, form vesicles with a higher number of lamellae.
Unitat de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Catalonia, Spain.
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Armengol
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Estelrich
D015502:Absorptiometry, Photon; D004355:Drug Stability; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D010316:Particle Size; D013696:Temperature
D005452:Fluoresceins; D005456:Fluorescent Dyes; D008055:Lipids; D008081:Liposomes; C024098:6-carboxyfluorescein