title: Oral absorption mechanism and anti-angiogenesis effect of taurocholic acid-linked heparin-docetaxel conjugates.
abstract: Oral delivery is the preferred route to deliver therapeutics via nanoparticles due to ease of administration and patient acceptance. Here, we report on the findings of the absorption pathway of taurocholic acid (TCA)-linked heparin and docetaxel (DTX) conjugate, which we refer to as HDTA. We studied the oral absorption of HDTA using a Caco-2 cell transport system and an animal model. We have also used other absorption enhancers, such as ethylene glycol tetraacetic acid (EGTA), or inhibitors, such as sodium azide, to compare the relative permeability of HDTA conjugates. In vivo comparative studies were conducted using free TCA as a pre-administration and exhibited the maximum absorption site of the organ after oral administration of HDTA conjugates. HDTA was found to be absorbed mainly in the ileum and Caco-2 cell monolayer through passive diffusion and bile acid transporters. High fluorescence intensity of HDTA in mice came from the ileum, and it was eliminated from the body through colon. This novel formulation could be further investigated by clinical trials to find the prospect of oral anti-cancer drug delivery through anti-angiogenic treatment strategies.
authors.affiliation: Department of Green Bioengineering, Korea National University of Transportation, Chungju, 380-702, Republic of Korea.
authors.forename: Zehedina
authors.initials: Z
authors.lastname: Khatun
authors.affiliation: Department of Polymer Science and Engineering, Korea National University of Transportation, Chungju, 380-702, Republic of Korea; Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, University of Utah, Salt Lake City, 84112, USA.
authors.lastname: Nurunnabi
authors.affiliation: Department of Otolaryngology, Head & Neck Surgery, The Catholic University of Korea, College of Medicine Uijeongbu St. Mary's Hospital, Kyunggi-Do 480-717, Republic of Korea. Electronic address: entckj@catholic.ac.kr.
authors.forename: Kwang Jae
authors.initials: KJ
authors.lastname: Cho
authors.affiliation: College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Youngro
authors.initials: Y
authors.lastname: Byun
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, University of Utah, Salt Lake City, 84112, USA.
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
authors.affiliation: Department of Green Bioengineering, Korea National University of Transportation, Chungju, 380-702, Republic of Korea; Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju, 380-702, Republic of Korea. Electronic address: leeyk@ut.ac.kr.
authors.forename: Yong-kyu
authors.initials: YK
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018938:Caco-2 Cells; D002478:Cells, Cultured; D000077143:Docetaxel; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006493:Heparin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D013656:Taurocholic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D043823:Taxoids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D020533:Angiogenesis Inhibitors; D043823:Taxoids; D042461:Vascular Endothelial Growth Factor A; D000077143:Docetaxel; D013656:Taurocholic Acid; D006493:Heparin; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Anti-angiogenesis; Bile acid transporters; Oral delivery; Taurocholic acid