Title : Formulation of liposomal doxorubicin modified with Bombesin peptide for selective targeting of GRP receptors over-expressed by cancer cells
The presentation concerns the obtainment of liposomal doxorubicin in which liposomes are externally modified with a targeting peptide able to drive liposomal doxorubicin in a selective way on membrane receptors over expressed in tumours. We have developed a kit containing a first vial filled with a sterile, translucent, red dispersion of the liposomal doxorubicin drug; a second vial filled with a modified phospholipid with a reactive function such as DSPE-Peg-maleimide in lyophilized form; and a third vial filled with a peptide modified with an appropriate reactive function, in a 1:1 stoichiometric amount respect to compound 1 and in lyophilized form. The choose peptide is a stable analogue of 1-9 Bombesin peptide; it is very stable in serum, maintains high specificity, with nanomolar affinity, toward GRP receptors over-expressed by cancer cells, and it acts as a bombesin antagonist, thus it does not interfere with biological pathways promoted by the bombesin peptide. Its efficacy in selective targeting of GRP receptors has been efficiently demonstrated in vitro and in vivo by nuclear medicine experiments, also when the peptide sequence is modified, as happens in peptide-liposome preparations, on its N-terminus. Results of animal studies concerning the in vivo use of liposomal doxorubicin modified with the targeting bombesin peptide will be presented; they clearly indicate that in mice treated with the kit product (i.e: Doxil modified with the Bombesin analog) tumor growth is absent and in some cases tumor regression is observed, with an improved efficacy respect to mice treated with non-modified Doxil or with non-liposomal Doxorubicin.
•The audience will benefit of new efficient methods for preparation of liposomal drugs modified with targeting agents such as peptides and antibodies.
•We will provide practical solutions to overcome technologic problems for the preparation of specific liposomal drugs ready to use in clinical studies and in human therapy.
•Moreover the audience will know the importance of targeting peptide receptors in different human tumors with more emphasis on the over-expression of bombesin receptors in different malignances such as prostate, ovarian and breast cancers.