Abstract:

The leucine zipper lipopeptide is a dimer composed of two lipopeptides with α-helical structures that interact through hydrophobic forces. When heated to its phase transition temperature, the helixes unwind and form a disordered conformation. Based on the thermo-sensitivity of these leucine zipper lipopeptides, we designed and synthesized a series of zipper-structured lipopeptides and then mixed them with lipids to form thermo-sensitive hybrid liposomes. Circular dichroism was used to investigate the secondary structure of the lipopeptides anchored in the liposomal bilayer. Dynamic light scattering measurements were used to assess the diameters and zeta potentials of the liposomes. Fluorescence polarization was measured to study the fluidity of the liposomal bilayer. An ultraviolet spectrophotometer was used to stimulate Doxorubicin (DOX) release in vitro at 37.0 and 45.0℃. We found that Lp-Lipo (hybrid of lipopeptide and liposome) displayed higher thermosensitivity than pure liposome. The cholesterol content and fluidity of the liposomal bilayer affected the thermocontrolled on-off switch of the lipopeptides. Lp-Lipo shows great potential as a novel thermo-sensitive drug carrier.

Key words: Leucine, Zipper-structured lipopeptide, Liposome, Thermo-sensitivity, Drug carrier