Interfacial interactions of hydrophobic peptides with lipid bilayers.

Four hydrophobic laminin-related peptides and their corresponding parent peptides were synthesized to use them to target liposomes to tumoral cells. The peptide sequence was YIGSR((NH(2))), and hydrophobic residues linked to the alpha-amino terminal end were decanoyl, myristoyl, stearoyl, and cholesteryl-succinoyl. Before use in biological systems, a physicochemical study was carried out in order to determine their interaction with DPPC bilayers that could compromise both the toxicity and the stability of liposomal preparations. The experiments were based on DSC, fluorescence polarization, outer-membrane destabilization, and vesicle leakage. These peptides showed in general a low interaction with the vesicles, promoting in all cases the rigidification of bilayers. This lack of strong disturbances in the ordered state of phospholipid molecules seems more likely due to the similarity of peptide acyl chains with those of lipids than to the absence of interactions. The bulkiness of cholesteryl derivative as well as its tendency toward aggregation resulted in weak interaction levels except in thermograms. The binding of peptides to the surface of liposomes loaded with doxorubicin resulted in preparations with good entrapment yields and small size, required for long circulating vesicles (especially for the myristoyl derivative). The alternative method based on the reaction of parent peptide to the surface of liposomes through an amide linkage was slightly more efficient when the peptide was linked to the carboxy-terminal end of the DSPE-PEG-COOH-containing liposomes. Nevertheless, the final decision must be made with the simplicity of the procedure and reduction in losses during all the steps of the processes taken into consideration.