title: 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.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Liaoning 110016, China.
authors.forename: Baohua
authors.initials: B
authors.lastname: Niu
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Liaoning 110016, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: He
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Liaoning 110016, China.
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Bao
authors.affiliation: School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China. Electronic address: ypli@simm.ac.cn.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D058612:Nanodiamonds / Q000737:chemistry*; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control*; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077157:Sorafenib; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D058612:Nanodiamonds; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
keywords: Cancer metastasis; Gastric cancer; Nanodiamond; Oral delivery; Sorafenib