title: Pharmacokinetics and tissue distribution study in mice of triptolide-loaded lipid emulsion and accumulation effect on pancreas.
abstract: Triptolide (TP) shows strong anti-tumor activities on various cancer cells, especially on pancreatic cancer. TP inhibits HSP70 expression leading to cell death in pancreatic cancer cells and induces cell death by apoptotic and autophagic pathways. In order to increase the therapeutic index of TP, a novel intravenous TP-loaded delivery system, TP-loaded lipid emulsion (TP-LE), has been developed to treat solid tumor. In the present study, the preparation and characterization of TP-LE were described. The pharmacokinetics and tissue distribution study of TP-LE in mice were also evaluated. Results demonstrated that TP-LE had an average particle size of 154.6 nm, entrapment efficiency (EE%) of 87%, zeta potential of -0.903 mV and autoclaved stability. The pharmacokinetic study showed that blood concentrations of both TP-LE and TP reached a maximum at the end of intravenous administration (1.25 mg/kg) and declined rapidly within the first 10 min with a mean residence time (MRT) of about 10 min. In the tissue distribution study, a preferential accumulation and longer residence time of drug in pancreas were found in TP-LE. The AUC0-60min of TP-LE in pancreas was 2.19 times in comparison to free TP, suggesting that the use of TP-LE conferred improvements in biodistribution, accumulation and therapeutic efficacy in pancreas. Moreover, the concentrations of TP-LE in heart, lung and kidney were lower than that of the TP group, indicating the potential for reduced toxicity of TP-LE. Together, all the results show that TP-LE appears to be a promising formulation for using TP in treating cancer, and more specifically pancreatic cancer.
authors: a School of Chinese Medicines, Shenyang Pharmaceutical University , Shenyang , China .
authors: Xue
authors: X
authors: Li
authors: a School of Chinese Medicines, Shenyang Pharmaceutical University , Shenyang , China .
authors: Yuling
authors: Y
authors: Mao
authors: b Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China .
authors: Kai
authors: K
authors: Li
authors: b Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China .
authors: Tianyu
authors: T
authors: Shi
authors: c Department of Pharmaceutical and Food Science , Tonghua Normal University , Tonghua , China , and.
authors: Huimin
authors: H
authors: Yao
authors: d Department of Foreign Language , School of Social Sciences and Literary, Shenyang Pharmaceutical University , Shenyang , China.
authors: Jianhua
authors: J
authors: Yao
authors: b Department of Pharmaceutics , School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China .
authors: Shujun
authors: S
authors: Wang
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D004224:Diterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004852:Epoxy Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D010616:Phenanthrenes / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D004224:Diterpenes; D004337:Drug Carriers; D004852:Epoxy Compounds; D008055:Lipids; D010616:Phenanthrenes; C001899:triptolide
keywords: Lipid emulsion; pancreatic cancer; pharmacokinetics; tissue distribution; triptolide