title: Synthesis and In Vitro Evaluation of Thiolated Carrageenan.
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.
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, A-6020, Austria.
authors.forename: Wongsakorn
authors.initials: W
authors.lastname: Suchaoin
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, A-6020, Austria.
authors.forename: Sonja
authors.initials: S
authors.lastname: Bonengel
authors.affiliation: Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innsbruck, A-6020, Austria.
authors.forename: Shah
authors.initials: S
authors.lastname: Hussain
authors.affiliation: Institute of Analytical Chemistry and Radiochemistry, University of Innsbruck, Innsbruck, A-6020, Austria.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Huck
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, University of Innsbruck, Innsbruck, A-6020, Austria.
authors.forename: Benjamin N
authors.initials: BN
authors.lastname: Ma
authors.affiliation: Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innsbruck, A-6020, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D002351:Carrageenan / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents / Q000737:chemistry; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D049990:Membrane Transport Modulators / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D008970:Molecular Weight; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D012624:Seaweed / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D034421:Sus scrofa; D013890:Thiourea / Q000737:chemistry; D014783:Viscosity
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D002351:Carrageenan; D005765:Gastrointestinal Agents; D007202:Indicators and Reagents; D049990:Membrane Transport Modulators; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D013438:Sulfhydryl Compounds; D013890:Thiourea
keywords: Caco-2 cells; MRP; biomaterials; mucosal delivery; multidrug resistance transporters; polymer synthesis; polymers