Inhomogeneous crystal grain formation in DPPC-DSPC based thermosensitive liposomes determines content release kinetics
Abstract Thermosensitive liposomes (TSL) receive attention due to their rapid externally controlled drug release at transition temperature in combination with hyperthermia. This rapid release feature of TSL occurs when the liposome membrane is going through a phase change which results in numerous interfaces, at so-called crystal grain boundaries. Based on experience with TSLs, our group found that thermosensitive liposomes formulated by binary compositions of DPPC and DSPC at proper ratios are able to exhibit rapid release without incorporation of release-promoting components. The aim of this study was to understand the mechanism of rapid release from bi-component DPPC-DSPC based TSL. Based on the investigation of a series of TSLs formulated by different DPPC-DSPC ratios, and through the analysis of binary-phase diagrams of DPPC-DSPC TSLs, we conclude that inhomogeneous crystal grains are formed in bi-component TSL membranes rather than mono-component, thereby facilitating content release. The resulting inhomogeneous membrane pattern is affected by DPPC/DSPC ratio, i.e. this determines the number of interfaces between solid and liquid phases at transition temperature, which can be diminished by addition of cholesterol. At appropriate DPPC/DSPC ratio, substantive solid/liquid interfaces can be generated not only between membrane domains but also between crystal grains in each domain of the liposome membranes, therefore improving content release from the TSL at transition temperatures. Graphical abstract [DISPLAY OMISSION]
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