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Giancarlo Morelli

Speaker for pharma conferences europe-Giancarlo Morelli

Title: Formulation of Liposomal Doxorubicin modified with Bombesin Peptide for selective targeting of GRP Receptors over-expressed by Cancer Cells

Giancarlo Morelli

University of Naples Federico II, Italy

Biography

Giancarlo Morelli is full professor of Chemistry at Dept. of Pharmacy University of Naples “Federico II”. He is Director of a Research Center on Bioactive Peptides (CIRPeB) and President of the Italian Society of Peptides (ItPS). His research interest is in peptide chemistry; his researches are focused on different aspects of peptide science, particularly he studied application of new designed peptides for selective targeting of contrast agents for MRI or Nuclear Medicine and for drugs and liposomal drugs. Giancarlo Morelli is also Chairman of the International Workshops on Bioactive peptides organized in Naples every two years and now at the 15th edition. G. Morelli is author of more than 150 papers most of them concerning the development of Peptide Science.

Abstract

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.

Audience will learn:
•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.