Efficacy and tissue distribution of DHP107, an oral paclitaxel formulation

Wan Hong Jung, In Hyun Lee, Hak Kwak Young, Taek Park Young, Chin Sung Ha, Ick Chan Kwon, Hesson Chung

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 (Tmax = 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.

Original languageEnglish
Pages (from-to)3239-3247
Number of pages9
JournalMolecular Cancer Therapeutics
Volume6
Issue number12
DOIs
Publication statusPublished - 2007 Dec 1

Fingerprint

Tissue Distribution
Paclitaxel
Lipids
Gastrointestinal Tract
Polysorbates
Micelles
P-Glycoprotein
Tumor Burden
Solubility
Intestines
Tail
Microscopy
Veins
Spleen
Epithelium
Endothelial Cells
High Pressure Liquid Chromatography
Staining and Labeling
Light
Lung

ASJC Scopus subject areas

  • Oncology
  • Drug Discovery
  • Pharmacology

Cite this

Jung, W. H., Lee, I. H., Young, H. K., Young, T. P., Ha, C. S., Kwon, I. C., & Chung, H. (2007). Efficacy and tissue distribution of DHP107, an oral paclitaxel formulation. Molecular Cancer Therapeutics, 6(12), 3239-3247. https://doi.org/10.1158/1535-7163.MCT-07-0261

Efficacy and tissue distribution of DHP107, an oral paclitaxel formulation. / Jung, Wan Hong; Lee, In Hyun; Young, Hak Kwak; Young, Taek Park; Ha, Chin Sung; Kwon, Ick Chan; Chung, Hesson.

In: Molecular Cancer Therapeutics, Vol. 6, No. 12, 01.12.2007, p. 3239-3247.

Research output: Contribution to journalArticle

Jung, WH, Lee, IH, Young, HK, Young, TP, Ha, CS, Kwon, IC & Chung, H 2007, 'Efficacy and tissue distribution of DHP107, an oral paclitaxel formulation', Molecular Cancer Therapeutics, vol. 6, no. 12, pp. 3239-3247. https://doi.org/10.1158/1535-7163.MCT-07-0261
Jung, Wan Hong ; Lee, In Hyun ; Young, Hak Kwak ; Young, Taek Park ; Ha, Chin Sung ; Kwon, Ick Chan ; Chung, Hesson. / Efficacy and tissue distribution of DHP107, an oral paclitaxel formulation. In: Molecular Cancer Therapeutics. 2007 ; Vol. 6, No. 12. pp. 3239-3247.
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