Rita Cortesi

University of Ferrara, Italy

Title: Can a proper physical characterization of lipid nanoparticles provide accurate information's on their performance?

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Biography

Rita Cortesi graduated in Pharmaceutical Chemistry and Technology and reached PhD in Pharmaceutical Sciences at Ferrara University. She attended a HMC Post-doc fellowship at Pharmaceutical Sciences Department of Nottingham University in 1995, and stayed at Ferrara University as assistant professor up to 2008 when she became associate professor. In 2014 she obtained the qualification on role of Full Professor on Pharmaceutical Technology. Her work focuses on pharmaceutical nanotechnology strategies. Other interests are on the use of natural antioxidant molecules for cosmetic application. She is the author of over 150 scientific papers considering articles in international journals, book chapters and patents.

Abstract

Cisplatin, carboplatin and oxaliplatin (OXA) are widely used in chemotherapy. However, their clinical benefits are limited by side-effects attributed to the reactivity of these Pt(II) compounds and acquired resistance. Pt(IV) complexes with two different axial groups may have advantages over the reactive Pt(II) species. They are inert in plasma, reach cancerous lesions in their Pt(IV) form, and activate their Pt(II) analogs inside the cancerous cells. Unfortunately, clinical evaluation of Platinum(IV) complexes showed rapid elimination, less or equal efficacy than Pt (II) drugs. Therefore, no Pt(IV) drug has reached the market. We synthesized oxaliplatin palmitate acetate (OPA), a novel Pt(IV) chemical entity derived from OXA and containing both lipophilic and hydrophilic axial ligands. OPA was found 20 times more efficient in killing various cancer cells than OXA. Furthermore, OPA demonstrated significantly higher tumour growth inhibition than OXA in orthotopic and xenograft mice tumour models of ovarian, pancreatic, lung and liver. However, OPA was also eliminated before cellular uptake. OPA was incorporated in PEGylated liposomes to overcome this drawback to optimize therapeutic performance. In vitro studies showed OPA-loaded liposomes retain OPA potency against di?erent cancer cell lines.

Furthermore, liposomes altered PK parameters and biodistribution patterns favouring the liposome formulations and significantly extended the systemic exposure. Intravenous administration of OPA liposomes (60 mg/kg, twice weekly) demonstrated delayed response and higher survival than cisplatin in a mouse liver xenograft model (Hep-3B). Furthermore, in two identical orthotopic intraperitoneal models of metastatic ovarian cancer (SKOV3-luc-D3), OPA liposomes were administered intravenously at 15, and 30 mg/kg (twice weekly) exhibited delayed response and higher survival compared to Avastin. At the same time, a combination of OPA and Avastin showed a significant synergistic effect enlightening the potential of OPA liposomes in the treatment of various cancers.