Synthesis of RGD containing peptides. Comparative study of their incorporation to the surface of 5-fluoruridine loaded liposomes

The synthesis on solid phase of a peptide sequence (GGRGRS) related to an integrin adhesion site as well as the preparation of some hydrophobic derivatives is described. The incorporation of these peptides to the surface of liposomes was carried out either through the NGPE (N-glutaryl dipalmitoyl phosphatidyl chorine) carboxyl-group or mixing hydrophobic peptide derivatives with lipids since the beginning of the process. The influence of these factors on the entrapment yield of 5-FUR (5-fluorouridine) was determined. Best results, calculated as percentage of drug encapsulation, were obtained when the peptide was linked to preformed liposomes via an NGPE-amide bond. On the contrary, the presence of these hydrophobic peptides on the bilayers decreases the overall yield of encapsulation of 5-FUR. Nevertheless, considering drug/lipid relationship and scaling-up requirements it seems that the use of myristoyl peptide derivative should be the procedure of choice. Physicochemical studies carried out with the peptides indicated that the presence of hydrophobic moieties linked to the parent peptide increases the tendency to self aggregation as detected through fluorescence studies using DPH (1, 6 diphenyl hexatriene) as marker, reducing in this way the efficiency of incorporation of hydrophobic peptides to the surface of liposomes.