Abstract
The aim of this study was to generate and characterize a thiolated carrageenan. Thiolated carrageenan (carrageenan-SH) was synthesized from kappa (κ)- and iota (ι)-carrageenan by bromine replacement of the hydroxyl moieties followed by substitution to thiol groups using thiourea. Thiolated κ- and ι-carrageenan exhibited 176.57 ± 20.11 and 109.51 ± 18.26 μmol thiol groups per gram polymer, respectively. The resazurin test in Caco-2 cells revealed no toxic effect of both thiolated carrageenans at a concentration below 0.1% (w/v). Regarding efflux pump inhibitory effect, cellular accumulation of multidrug-resistance protein 2 substrate, sulforhodamine 101, was 1.38- and 1.35-fold increased in cells treated with thiolated κ- and ι-carrageenan, respectively. Modification of κ- and ι-carrageenan led to 3.9- and 2.0-fold increase in dynamic viscosity of mucus-thiolated carrageenan mixture within 4 h. Furthermore, residence time of κ- and ι-carrageenan-SH on porcine intestinal mucosa was 6.4- and 1.8-fold prolonged, respectively, as demonstrated by rotating cylinder method, indicating improved mucoadhesive properties. Hence, thiolation of carrageenans led to novel pharmaceutical excipients for various applications.
Keywords:
Caco-2 cells; MRP; biomaterials; mucosal delivery; multidrug resistance transporters; polymer synthesis; polymers.
© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Antiviral Agents / adverse effects
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology*
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Caco-2 Cells
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Carrageenan / adverse effects
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Carrageenan / chemistry
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Carrageenan / pharmacology*
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Cell Survival / drug effects
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Enterocytes / drug effects
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Enterocytes / metabolism
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Gastrointestinal Agents / adverse effects
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Gastrointestinal Agents / chemistry
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Gastrointestinal Agents / pharmacology*
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Humans
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Indicators and Reagents / chemistry
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Intestinal Absorption / drug effects*
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Intestinal Mucosa / drug effects*
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Intestinal Mucosa / metabolism
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Membrane Transport Modulators / adverse effects
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Membrane Transport Modulators / chemistry
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Membrane Transport Modulators / pharmacology
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Molecular Weight
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Multidrug Resistance-Associated Protein 2
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Multidrug Resistance-Associated Proteins / antagonists & inhibitors
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Multidrug Resistance-Associated Proteins / metabolism
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Seaweed / chemistry
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Sulfhydryl Compounds / adverse effects
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Sulfhydryl Compounds / chemistry
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Sulfhydryl Compounds / pharmacology*
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Sus scrofa
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Thiourea / chemistry
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Viscosity
Substances
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Antineoplastic Agents
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Antiviral Agents
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Gastrointestinal Agents
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Indicators and Reagents
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Membrane Transport Modulators
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Multidrug Resistance-Associated Protein 2
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Multidrug Resistance-Associated Proteins
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Sulfhydryl Compounds
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Carrageenan
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Thiourea