title: Vitamin B₁₂ and derivatives--In vitro permeation studies across Caco-2 cell monolayers and freshly excised rat intestinal mucosa.
abstract: The purpose of this study was to compare the intestinal permeation of vitamin B12 and various derivatives thereof. Permeation behavior and cytotoxicity of four derivatives (coenzyme B12, hydroxocobalamin, methylcobalamin and 4-ethylphenylcobalamin) in comparison to vitamin B12 were evaluated in two different in vitro models, Caco-2 cells and freshly excised rat intestinal mucosa. Resazurin assay was used to evaluate cytotoxicity of the test substances. All test compounds were used at a concentration of 200 μg/ml. Permeation experiments were carried out for 3h and test compounds were quantified via reversed phase high performance liquid chromatography (HPLC). Cytotoxicity studies showed all test compounds are not toxic to cells. HPLC analyses of test compounds revealed the following rank order of increasing hydrophobicity: hydroxocobalamin<vitamin B12<coenzyme B12<methylcobalamin<4-ethylphenylcobalamin. Apparent permeability coefficients of coenzyme B12, hydroxocobalamin, methylcobalamin and 4-ethylphenylcobalamin were 10.2, 0.3, 9.4 and 31.3 fold of vitamin B12 on Caco-2 cells while 0.2, 0.4, 2.6 and 1.9 fold of vitamin B12 on rat intestine, respectively. As various vitamin B12 derivatives showed a significantly higher permeation coefficient than vitamin B12, the use of certain derivatives might be a promising strategy for oral vitamin B12 substitution.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Kesinee
authors.initials: K
authors.lastname: Netsomboon
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Feßler
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Lena
authors.initials: L
authors.lastname: Erletz
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Felix
authors.initials: F
authors.lastname: Prüfert
authors.affiliation: Institute of Organic Chemistry and Centre of Molecular Biosciences, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Ruetz
authors.affiliation: Institute of Organic Chemistry and Centre of Molecular Biosciences, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kieninger
authors.affiliation: Institute of Organic Chemistry and Centre of Molecular Biosciences, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kräutler
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D015394:Molecular Structure; D010539:Permeability; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D014805:Vitamin B 12
keywords: 4-Ethylphenylcobalamin; Coenzyme B(12); Hydroxocobalamin; Methylcobalamin; Vitamin B(12)