"Liver Smart Drug" project aims to advance innovative technologies to develope and validate, in the industrial field, macromolecular nanostructured systems to effectively treat liver cancer, in terms of improving the bioavailability of active ingredients, improving the therapeutic index and controlled and targeted release.
The project will start from previous research results obtained through the PON project - HUMAN HEALTH AND BIOTECHNOLOGY sector, Project "HIPPOCRATES PON02_00355_2964193: Development of Micro and Nano-Technologies and Advanced Systems for Human Health", presented to the MIUR by the Sicily Micro and Nano Systems District (implementing subject) and approved for funding with DM Prot. 427/RIC of 19.07.2012), that have allowed to obtain excellent results in the treatment of liver cancer through advanced prototypes of molecular nanosystems based on a biocompatible synthetic polyamine acid, (SmartDrug for Liver – LSD1) that have been the subject of a patent filing (Inventors: G. Pitarresi, M. Cervello, A. Azzolina, R. Puleio, G.R. Loria, S. Puleo, G. Giammona "Nanoparticles for the controlled release of Sorafenib" Application number: 102017000017594, submission date 16/02/2017, property: Distretto Tecnologico Sicilia Micro e Nano Sistemi S.C.A.R.L.).
In detail, nanoparticles based on a brush copolymer marked PHEA-BIB-ButMA (PBB) were made and characterized, synthesized in turn by Atom Transfer Radical Polymerization (ATRP) starting from a,b-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) and butylmethacrylate. Both empty and Sorafenib-containing PBB nanoparticles were prepared using the dialysis method and showed a spherical shape, size of about 200 nm, negative zeta potential and the ability to allow a prolonged release of Sorafenib in physiological fluid. These nanoparticles are stable even after storage for three months at different temperatures.
In vitro studies have shown better efficacy of PBB nanoparticles containing Sorafenib compared to the free drug. In vivo studies in a xenograft model of liver cancer implanted in mice have shown a significant increase in the efficacy of such sorafenib-containing nanoparticles in inhibiting tumor growth compared to free Sorafenib, after intraperitoneal administration. In addition, in vivo biodistribution studies have shown that PBB nanoparticles containing Sorafenib accumulate preferentially in the tumor solid mass while their presence in other organs is lower than that shown by the non-conveyed drug. Therefore, the results obtained from these studies suggest that these nanoparticles represent excellent potential candidates for the direct release of Sorafenib in the treatment of HCC.
The ultimate goal will be the engineering and optimization of these systems up to their technological validation in the industrial field, in order to attract capital investments in the Sicily region by pharmaceutical multinationals such as Bayer which is the pharmaceutical company that has Sorafenib on the market.