Sorafenib is an orally active multikinase inhibitor and it is only anticancer drug that has proved to significantly prolong the survival time in patients with advanced hepatocellular carcinoma (HCC), when not candidates for potentially curative treatment or transarterial chemoembolization. However, sorafenib is characterized by severe toxic side effects limiting the possible therapeutic response (1,2). Nanoparticle (NP) based approaches offer a valuable alternative for cancer drug delivery, functioning as a carrier for entry through fenestrations in tumor vasculature, thus allowing direct cell access and ensuring the accumulation of high concentrations of drug to the targeted cancer cell, with a concomitant reduced toxicity of normal tissue. In this contest, superparamagnetic iron oxide NPs (SPIONs) are very attractive for delivery of therapeutic agents as they have been reported to enhance the drug delivery to specific locations in the body through the application of an external magnetic field (3,4). Here, solid lipid NPs (SLN) containing sorafenib and SPIONs have been prepared by a hot homogenization technique using cetyl palmitate as lipid matrix and polyethylene glycol modified phospholipids (PEG lipids), in order to achieve a PEG-based anti-fouling coating on SLN surface. These nanoformulations, thoroughly investigated by means of complementary techniques, have finally resulted effective drug delivery magnetic nanovectors with good stability in aqueous medium and high drug encapsulation efficiency (% EE>90%). In addition, the relaxometric characterization has proven that the magnetic SLN loaded with sorafenib are also very efficient contrast agents, with a great potential in magnetic resonance imaging (MRI) technique. The proposed magnetic SLNs loaded with sorafenib represent promising candidates for image guided and magnetic targeting of sorafenib to liver towards an efficacious treatment of HCC.
Magnetic Solid Lipid Nanoparticles for Magnetically Targeted Delivery of Sorafenib for Treatment of Hepatocellular Carcinoma
Fabio Vischio;Nicoletta Depalo;Marinella Striccoli;
2017
Abstract
Sorafenib is an orally active multikinase inhibitor and it is only anticancer drug that has proved to significantly prolong the survival time in patients with advanced hepatocellular carcinoma (HCC), when not candidates for potentially curative treatment or transarterial chemoembolization. However, sorafenib is characterized by severe toxic side effects limiting the possible therapeutic response (1,2). Nanoparticle (NP) based approaches offer a valuable alternative for cancer drug delivery, functioning as a carrier for entry through fenestrations in tumor vasculature, thus allowing direct cell access and ensuring the accumulation of high concentrations of drug to the targeted cancer cell, with a concomitant reduced toxicity of normal tissue. In this contest, superparamagnetic iron oxide NPs (SPIONs) are very attractive for delivery of therapeutic agents as they have been reported to enhance the drug delivery to specific locations in the body through the application of an external magnetic field (3,4). Here, solid lipid NPs (SLN) containing sorafenib and SPIONs have been prepared by a hot homogenization technique using cetyl palmitate as lipid matrix and polyethylene glycol modified phospholipids (PEG lipids), in order to achieve a PEG-based anti-fouling coating on SLN surface. These nanoformulations, thoroughly investigated by means of complementary techniques, have finally resulted effective drug delivery magnetic nanovectors with good stability in aqueous medium and high drug encapsulation efficiency (% EE>90%). In addition, the relaxometric characterization has proven that the magnetic SLN loaded with sorafenib are also very efficient contrast agents, with a great potential in magnetic resonance imaging (MRI) technique. The proposed magnetic SLNs loaded with sorafenib represent promising candidates for image guided and magnetic targeting of sorafenib to liver towards an efficacious treatment of HCC.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
