This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hong, J. W. Articles by Chung, H. Search for Related Content PubMed PubMed Citation Articles by Hong, J. W. Articles by Chung, H.

Research Articles: Therapeutics, Targets, and Development

Efficacy and tissue distribution of DHP107, an oral paclitaxel formulation

¹ Center for Chemoinformatics Research and ² Biomedical Research Center, Korea Institute of Science and Technology; ³ Graduate School of Biotechnology, Korea University, Seoul, Korea; and ⁴ Central Research Center, Daehwa Pharmaceutical Co. Ltd., Hoengseong-gun, Gangwon-do, Korea

Requests for reprints: Hesson Chung, Center for Chemoinformatics Research, Life Sciences Research Division, Korea Institute of Science and Technology, Hawolgok-dong, Sungbuk-gu, Seoul 136-791, Korea. Phone: 82-2958-5922; Fax: 82-2958-5909. E-mail: heschung{at}kist.re.kr

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-µm 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. [Mol Cancer Ther 2007;6(12):3239–47]

Grant support: "High Efficiency Anticancer Drug Delivery System Development Program" at the Ministry of Commerce, Industry and Energy in South Korea, grant no. B49-990-5411-04-1-3 and KIST grant.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

⁵ Submitted for publication.

⁶ Submitted for publication.

⁷ Submitted for publication.

Received 4/10/07; revised 8/ 9/07; accepted 10/ 9/07.