Multilayer-Coated Liquid Crystalline Nanoparticles for Effective Sorafenib Delivery to Hepatocellular Carcinoma

다국어 초록 (Multilingual Abstract)

<P>Hepatocellular carcinoma is one of the most common cancers in adults and develops due to activation of oncogenes and inactivation of tumor suppressor genes. Sorafenib (SF) is a U.S. Food and Drug Administration (FDA) approved drug for the treatment of hepatocellular carcinoma. However, its clinical use is limited by its poor aqueous solubility and undesirable side effects. Monoolein-based liquid crystalline nanoparticles (LCN) are self-assembled structures that have been determined as promising drug-delivery vehicles. Therefore, the main aim of this study was to prepare layer-by-layer (LbL) polymer-assembled SF-loaded LCNs (LbL-LCN/SF) for effective delivery of SF to hepatocellular carcinoma. Results revealed that LbL-LCN/SF presented optimum particle size (∼165 nm) and polydispersity index (PDI, ∼0.14) with appropriate polymer layer assembly confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM). Furthermore, LbL-LCN/SF effectively controlled burst release and exhibited pH-sensitive release of SF, thereby increasing drug release in the acidic microenvironment of tumor cells. Compared to free SF and bare LCN, the hemolytic activity of LbL-LCN/SF was significantly reduced (<I>p</I> < 0.01). Interestingly, LbL-LCN/SF was more cytotoxic to HepG2 cells than the free drug was. Additionally, high cellular uptake and greater apoptotic effects of LbL-LCN/SF in HepG2 cells indicates superior antitumor effects. Therefore, LbL-LCN/SF is a potentially effective formulation for hepatocellular carcinoma.</P><P><B>Graphic Abstract</B>
<IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/aamick/2015/aamick.2015.7.issue-36/acsami.5b06203/production/images/medium/am-2015-062032_0010.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/am5b06203'>ACS Electronic Supporting Info</A></P>