The physicochemical and release properties of non-extruded 'multilamellar' and small sonicated and extruded 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) liposomes containing hydrophobic drug dexamethasone were investigated. Non-extruded liposomes had similar diameter, however dexamethasone encapsulation decreased with increase in lipid chain length. Dexamethasone destabilized the liposome membranes as indicated by decrease in enthalpy and increase in the peak width of the main transition. Based on calorimetric analysis, it appeared that dexamethasone and cholesterol were heterogeneously distributed in the non-extruded liposomes. Sonication and extrusion reduced the diameter (DSPC>DPPC>DMPC) and decreased drug encapsulation (approximately 50%). Cholesterol incorporation decreased drug encapsulation in both extruded and non-extruded DMPC liposomes which appeared to be due to structural similarities between cholesterol and dexamethasone. Incorporation of dexamethasone and cholesterol in the same DMPC liposomes caused a marked perturbation in the phase transition. Dexamethasone release from extruded liposomes was fast, while non-extruded liposomes showed slower release. Release was fastest from DMPC liposomes and slowest from liposomes of high phase transition lipid DSPC. Incorporation of cholesterol did not decrease release from DMPC liposomes. These results indicated that change in the physicochemical properties and the phase transition behavior of liposomes, due to processing as well as incorporation of hydrophobic drug dexamethasone, changed their release properties.
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