In vivo biodistribution, biocompatibility, and efficacy of sorafenib-loaded lipid-based nanosuspensions evaluated experimentally in cancer.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. In this study, sorafenib-loaded lipid-based nanosuspensions (sorafenib-LNS) were first developed as an intravenous injectable formulation to increase the efficacy of sorafenib against HCC. LNS were used as nanocarriers for sorafenib owing to their desired features in increasing the solubility and dissolution velocity, improving the bioavailability of sorafenib. Sorafenib-LNS were prepared by nanoprecipitation and consisted of spherical particles with a uniform size distribution (164.5 nm, polydispersity index =0.202) and negative zeta potential (-11.0 mV). The drug loading (DL) was 10.55%±0.16%. Sorafenib-LNS showed higher in vitro cytotoxicity than sorafenib against HepG2 cells (P<0.05) and Bel-7402 cells (P<0.05). The in vivo biodistribution, biocompatibility, and antitumor efficacy of sorafenib-LNS were evaluated in H22-bearing liver cancer xenograft murine model. The results showed that sorafenib-LNS (9 mg/kg) exhibited significantly higher antitumor efficacy by reducing the tumor volume compared with the sorafenib oral group (18 mg/kg, P<0.05) and sorafenib injection group (9 mg/kg, P<0.05). Furthermore, the results of the in vivo biodistribution experiments demonstrated that sorafenib-LNS injected into H22 tumor-bearing mice exhibited increased accumulation in the tumor tissue, which was confirmed by in vivo imaging. In the current experimental conditions, sorafenib-LNS did not show significant toxicity both in vitro and in vivo. These results suggest that sorafenib-LNS are a promising nanomedicine for treating HCC.
Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, Shandong Province, People's Republic of China.
Shaomei
S
Yang
Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, Shandong Province, People's Republic of China.
Bo
B
Zhang
Shandong Provincial Key Laboratory of Neuroprotective Drug, Jinan, Shandong Province, People's Republic of China.
Xiaowei
X
Gong
Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, Shandong Province, People's Republic of China.
Tianqi
T
Wang
Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, Shandong Province, People's Republic of China.
Yongjun
Y
Liu
Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, Shandong Province, People's Republic of China.
Na
N
Zhang
D061605:Administration, Intravenous; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D065546:Drug Liberation; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008055:Lipids / Q000737:chemistry*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits; D000077157:Sorafenib; D013535:Suspensions; D014018:Tissue Distribution / Q000187:drug effects; D016896:Treatment Outcome; D014680:Veins / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D008055:Lipids; D010671:Phenylurea Compounds; D013535:Suspensions; D009536:Niacinamide; D000077157:Sorafenib
HCC; antitumor effect; distribution; lipid-based nanosuspensions; sorafenib