Pectin-cysteine conjugate: synthesis and in-vitro evaluation of its potential for drug delivery

Authors

  • Sayeh Majzoob,

    1. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran.
    2. Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Josef Möller Haus, A-6020 Innsbruck, Austria.
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  • Fatemeh Atyabi,

    1. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran.
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  • Farid Dorkoosh,

    1. Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran.
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  • Krum Kafedjiiski,

    1. Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Josef Möller Haus, A-6020 Innsbruck, Austria.
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  • Brigitta Loretz,

    1. Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Josef Möller Haus, A-6020 Innsbruck, Austria.
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  • Andreas Bernkop-Schnürch

    Corresponding author
    1. Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Josef Möller Haus, A-6020 Innsbruck, Austria.
      Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Josef Möller Haus, A-6020 Innsbruck, Austria. E-mail: andreas.bernkop@uibk.ac.at
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Department of Pharmaceutical Technology, Institute of Pharmacy, Leopold-Franzens-University Innsbruck, Innrain 52, Josef Möller Haus, A-6020 Innsbruck, Austria. E-mail: andreas.bernkop@uibk.ac.at

Abstract

This study was aimed at improving certain properties of pectin by introduction of thiol moieties on the polymer. Thiolated pectin was synthesized by covalent attachment of cysteine. Pectin-cysteine conjugate was evaluated for its ability to be degraded by pectinolytic enzyme. The toxicity profile of the thiolated polymer in Caco-2-cells, its permeation enhancing effect and its mucoadhesive and swelling properties were studied. Moreover insulin-loaded hydrogel beads of the new polymer were examined for their stability in simulated gastrointestinal conditions and their drug release profile. The new polymer displayed 892.27 ± 68.68 μmol thiol groups immobilized per g polymer, and proved to have retained its biodegradability, upon addition of Pectinex Ultra SPL in-vitro, determined by viscosity measurements and titration method. Pectin-cysteine showed no severe toxicity in Caco-2 cells, as tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Moreover, the synthesized polymer exhibited a relative permeation enhancement ratio of 1.61 for sodium fluorescein, compared to unmodified pectin. Pectin-cysteine conjugate exhibited approximately 5-fold increased in in-vitro adhesion duration and significantly improved cohesive properties. Zinc pectin-cysteine beads showed improved stability in simulated gastrointestinal media; however, insulin release from these beads followed the same profile as unmodified zinc pectinate beads. Due to favourable safety and biodegradability profile, and improved cohesive and permeation-enhancing properties, pectin-cysteine might be a promising excipient in various transmucosal drug delivery systems.

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