title: Efficacy and tissue distribution of DHP107, an oral paclitaxel formulation.
abstract: Paclitaxel is indispensable in treating human cancers. Due to poor drug solubility and efflux systems in the gastrointestinal tract, peroral delivery of paclitaxel has been a significant challenge. We developed a mucoadhesive oral formulation (DHP107) that can directly and effectively deliver paclitaxel to intestinal endothelial cells without concomitant use of P-glycoprotein inhibitors. Here, we evaluated the tissue distribution of paclitaxel, the antitumor efficacy and the absorption mechanism of DHP107. DHP107, which contains 10 mg/mL of paclitaxel in a mixture of monoolein, tricarprylin, and Tween 80 was administered p.o. to female BALB/c mice at a 50 mg/kg dose. Diluted Taxol was administered via bolus tail-vein injection at 10 mg/kg as a control. Blood and tissue samples were harvested at various time points and analyzed by high-performance liquid chromatography. Tissue sections were observed using light microscopy after immunohistochemical and Oil Red O staining. By day 27, tumor volume after DHP107 and Taxol treatments was one-third of that in the untreated group. After p.o. administration, paclitaxel was widely distributed in various organs (T(max) = 2 h), especially liver, spleen, and lung. DHP107 was effectively absorbed through the intestinal lipid transport system. DHP107 changed spontaneously into <100-mum droplets and micelles in the intestine, which in turn adhered to mucoepithelial cells, were absorbed via lipid uptake mechanism, and formed lipid bodies in the epithelium. Paclitaxel in DHP107 was effectively absorbed through the gastrointestinal tract via lipid uptake mechanism and was distributed in various tissues. The detailed uptake mechanism is currently under investigation.
authors: Center for Chemoinformatics Research, Life Sciences Research Division, Korea Institute of Science and Technology, Hawolgok-dong, Sungbuk-gu, Seoul 136-791, Korea.
authors: Jung Wan
authors: JW
authors: Hong
authors: In-Hyun
authors: IH
authors: Lee
authors: Young Hak
authors: YH
authors: Kwak
authors: Young Taek
authors: YT
authors: Park
authors: Ha Chin
authors: HC
authors: Sung
authors: Ick Chan
authors: IC
authors: Kwon
authors: Hesson
authors: H
authors: Chung
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel