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Journal of controlled release : official journal of the Controlled Release Society v.247, 2017년, pp.64 - 72   SCI SCIE
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Inhomogeneous crystal grain formation in DPPC-DSPC based thermosensitive liposomes determines content release kinetics

Lu, Tao (Correspondence to: T. Lu, Laboratory Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus MC, Room Ee175, 3000CA Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands. ); ten Hagen, Timo L.M. (Correspondence to: T. L.M. ten Hagen, Laboratory Experimental Surgical Oncology, Section Surgical Oncology, Department of Surgery, Erasmus MC, Room Ee 0104a, PO Box 1738, 3000 DR Rotterdam, The Netherlands. );
  • 초록  

    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]


  • 주제어

    Thermosensitive liposome .   DPPC .   DSPC .   Inhomogeneous crystal grain .   Phase transition .   Release kinetics.  

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