The use of lipid-coated nanodiamond to improve bioavailability and efficacy of sorafenib in resisting metastasis of gastric cancer.

Abstract

The metastasis is one of the greatest challenges for successful cancer therapy. Herein, we report a lipid-coated nanodiamond (ND) system loading water-insoluble sorafenib (SND) to improve the bioavailability and efficacy on suppression of cancer metastasis. SND was homogenous nanoassemblies with the mean diameter of 127.6 ± 12.9 nm. Compared with the drug suspension, the sorafenib concentration in gastrointestinal (GI) tract and major organs was significantly increased by SND. Moreover, the oral bioavailability of sorafenib was greatly improved 7.64-fold by SND. However, the ND in SND could not be absorbed into the mucus of GI tract or distributed into major organs after oral administration. Furthermore, the sorafenib concentration in tumor tissue was markedly improved 14.95 folds by SND, and SND demonstrated an efficient and impressive tumor growth inhibition effect in tumor xenograft models. In particular, the metastasis of gastric cancer to distant organs of liver and kidney was remarkably suppressed by SND, which was verified by the detection of macroscopic metastatic nodules, histological examination and immunofluorescence measurements. Thereby, the lipid-coated ND could be a promising drug delivery platform for improving the oral bioavailability of lipophilic drugs and treatment of cancer metastasis.

• Authors: Zhiwen Zhang, Baohua Niu, Jian Chen, Xinyu He, Xiaoyue Bao, Jianhua Zhu, Haijun Yu, Yaping Li
• Journal: Biomaterials (Biomaterials) Vol. 35 Issue 15 Pg. 4565-72 (May 2014) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 24602567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Lipids
• Nanodiamonds
• Phenylurea Compounds
• Niacinamide
• Sorafenib

Topics

• Administration, Oral
• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Biological Availability
• Drug Carriers (chemistry)
• Humans
• Lipids (chemistry)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Nanodiamonds (chemistry)
• Neoplasm Metastasis (pathology, prevention & control)
• Niacinamide (administration & dosage, analogs & derivatives, pharmacokinetics, therapeutic use)
• Phenylurea Compounds (administration & dosage, pharmacokinetics, therapeutic use)
• Sorafenib
• Stomach (drug effects, pathology)
• Stomach Neoplasms (drug therapy, pathology)