Advanced hepatocellular carcinoma (HCC) is a clinical challenge with limited treatment options. The orally active multikinase inhibitor sorafenib is the only anticancer agent showing a survival benefit in these patients. As well as significant activity, sorafenib is characterized by severe toxic side effects limiting the possible therapeutic response (1). Nanoparticle (NP) based approaches offer a valuable alternative for cancer drug delivery, thus ensuring the accumulation of high concentrations of drug to the targeted cancer cell, with a concomitant reduced toxicity of normal tissue. 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 (2). Here, solid lipid NPs (SLNs) 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. 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 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.
Magnetically Targeted Delivery of Sorafenib to Liver Using Solid Lipid Nanoparticles for Treatment of Hepatocellular Carcinoma
Nicoletta Depalo;Fabio Vischio;Marinella Striccoli;
2017
Abstract
Advanced hepatocellular carcinoma (HCC) is a clinical challenge with limited treatment options. The orally active multikinase inhibitor sorafenib is the only anticancer agent showing a survival benefit in these patients. As well as significant activity, sorafenib is characterized by severe toxic side effects limiting the possible therapeutic response (1). Nanoparticle (NP) based approaches offer a valuable alternative for cancer drug delivery, thus ensuring the accumulation of high concentrations of drug to the targeted cancer cell, with a concomitant reduced toxicity of normal tissue. 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 (2). Here, solid lipid NPs (SLNs) 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. 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 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.
