title: Enhanced antitumor activity of realgar mediated by milling it to nanosize.
abstract: Realgar is a poorly water-soluble compound that exhibits poor bioavailability. To improve this, the authors reduced the particle size of realgar to nanoscale by high-energy ball milling and optimized the preparation process under which (realgar weight 40 g, milling time 9 hours, milling speed 38 Hz, milling temperature -20°C) realgar nanoparticles (NPs) with an average size of 78 ± 8.3 nm were prepared. The average particle size of realgar was characterized by laser scattering, and its apparent shape was observed by transmission electron microscopy and scanning electron microscopy. The solubility of realgar was enhanced after milling until the particles were in the nanoscale region without altering its properties, as confirmed by a scanning electron microscopy energy-dispersive spectrometer. Realgar NPs had higher cytotoxicity on the selected cell lines, namely human breast cancer (MCF7), human hepatoma (HepG2), and human lung cancer (A549) cell lines, than coarse realgar. In addition, a pharmacokinetics study performed in rats indicated that the relative bioavailability of realgar NPs was 216.9% compared with coarse realgar; a biodistribution study performed in mice showed that after intragastric administration of realgar NPs, higher arsenic concentration was reached in the tumor, heart, liver, spleen, lung, and kidney compared with the administration of coarse realgar, as confirmed by inductively coupled plasma mass spectrometry to determine the concentration of arsenic. This study indicated that high-energy ball milling is an effective way to reduce the average particle size of realgar, and compared with coarse realgar, the cytotoxicity and bioavailability of realgar NPs were significantly improved.
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors: Ye
authors: Y
authors: Tian
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, People's Republic of China ; Department of Pharmacy, 210th Hospital of People's Liberation Army, Dalian, People's Republic of China.
authors: Xiaobo
authors: X
authors: Wang
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, People's Republic of China ; Department of Pharmacy, 210th Hospital of People's Liberation Army, Dalian, People's Republic of China.
authors: Ronggang
authors: R
authors: Xi
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors: Weisan
authors: W
authors: Pan
authors: Department of Pharmacy, 210th Hospital of People's Liberation Army, Dalian, People's Republic of China.
authors: Shuang
authors: S
authors: Jiang
authors: Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.
authors: Zhao
authors: Z
authors: Li
authors: Department of Pharmaceutics, College of Pharmacy, Harbin Medical University, Harbin, People's Republic of China.
authors: Yu
authors: Y
authors: Zhao
authors: Department of Laboratory Medicine, Liaoning Institute for Food and Drug Control, Shenyang, People's Republic of China, People's Republic of China.
authors: Guanghui
authors: G
authors: Gao
authors: Department of Pharmacy, 210th Hospital of People's Liberation Army, Dalian, People's Republic of China.
authors: Dan
authors: D
authors: Liu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001152:Arsenicals / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D008516:Medicine, Chinese Traditional; D051379:Mice; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage* / Q000648:ultrastructure; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D013440:Sulfides; C058317:arsenic disulfide
keywords: biodistribution; cytotoxicity; high-energy ball milling; pharmacokinetics; realgar nanoparticles