Lipid nanocarrier for the treatment of hepatocellular carcinoma

Risultato della ricerca: Other


Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. Unlike most solid tumors the incidence and mortality of HCC have increased in the United States and Europe in the past decade. Most patients are diagnosed at advanced stages, so there is an urgent need for new systemic therapies [1,2].To improve the delivery of therapeutic agents to tumor cells in vivo it’s necessary to overcome several problems, such as drug resistance at the tumor level due to physiological barriers (non cellular based mechanism), drug resistance at the cellular level (cellular mechanism), drug distribution, biotransformation and clearance of anticancer drugs in the body. At the purpose to increase selectivity of drugs towards cancer cells while reducing their toxicity towards normal tissues, a promising strategy could be to entrap antitumor drugs into colloidal nanoparticles. Nanosystems may act as drug vehicles able to target tumor tissues or cells, protecting it from premature inactivation during its transport. At the tumor level the accumulation mechanism of intravenously injected nanoparticles relies on a passive diffusion or convection across the leaky hyperpermeable tumor vasculature [3-5].For the treatment of HCC several drugs are under development, but the only one with proven survival benefit is sorafenib. This agent is a multikinase inhibitor that blocks Raf signaling and VEGF, PDGF and c-Kit. It has antiproliferative and antiangiogenic activity and delays tumor progression [1,2].In order to produce a new colloidal system able to deliver this drug in the tumor tissue and decrease its side effects, nanostructured lipid carriers (NLCs) were developed using tripalmitin, Miglyol 812 and sorafenib. The obtained nanosystems were characterized in terms of size, polidispersity index, zeta potential and morphology using Scanning Electron Microscopy. Moreover, technological-pharmaceutical characterization of NLC was made. Stability studies showed that the systems were stable up to 60 days, while particle aggregation occurred after a period of storage of 90 days. Afterwards, for this reason, the same systems were prepared with the addition of two cryoprotectors (threalose and glycerol) before freezing and lyophilization. Finally, in vitro biological studies were carried out by MTS assays using human hepatocellular carcinoma HepG2, Hep3B, Huh7 and PLC/PRF/5 cells. Results obtained demonstrate an improved efficacy of sorafenib-loaded NLC compared to the free drug in Huh7 cells, whereas in HepG2 and PLC/PRF/5 cells sorafenib-loaded NLCs maintain an antitumor activity comparable to free drug. Considering that solid tumours present much more favourable conditions for preferential accumulation of colloidal sized drug delivery systems, sorafenib-loaded NLC can be useful for application in liver cancer therapy.[1] A. Forner, J.M. Llovet and J. Bruix, Lancet, 379, 1245 (2012). [2] M. Cervello, J.A. McCubrey, A. Cusimano, N. Lampiasi, A. Azzolina and G. Montalto, Oncotarget, 3, 236 (2012).[3] I. Brigger, C. Dubernet and P. Couvreur, Adv. Drug Del. Rev., 54, 631 (2002).[4] M.L. Bondì, A. Azzolina, E.F. Craparo, G. Capuano, N. Lampiasi , G. Giammona and M. Cervello, Curr. Nanoscience, 5, 39 (2009). [5] M.L. Bondì, E.F. Craparo, G. Giammona, M. Cervello, A. Azzolina, P. Diana, A. Martorana and G. Cirrincione, Drug Deliv., 14, 61 (2007).
Lingua originaleEnglish
Numero di pagine3
Stato di pubblicazionePublished - 2013

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