Ionotropic Gelation and Chemical Crosslinking as Tools to Obtain Gellan Gum-Based Beads with Mesalazine

<b>Introduction:</b> Many orally administered drugs are either unstable in the acidic environment of the stomach or cause moderate to severe side effects in the upper gastrointestinal tract (GIT). These limitations can reduce therapeutic efficacy, discourage patient compliance, worsen th...

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Main Authors: Piotr Gadziński, Agnieszka Skotnicka, Natalia Lisiak, Ewa Totoń, Błażej Rubiś, Ewa Florek, Dariusz T. Mlynarczyk, Mirosław Szybowicz, Ewelina Nowak, Tomasz Osmałek
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Language:English
Published: MDPI AG 2025-04-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/5/569
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author Piotr Gadziński
Agnieszka Skotnicka
Natalia Lisiak
Ewa Totoń
Błażej Rubiś
Ewa Florek
Dariusz T. Mlynarczyk
Mirosław Szybowicz
Ewelina Nowak
Tomasz Osmałek
author_facet Piotr Gadziński
Agnieszka Skotnicka
Natalia Lisiak
Ewa Totoń
Błażej Rubiś
Ewa Florek
Dariusz T. Mlynarczyk
Mirosław Szybowicz
Ewelina Nowak
Tomasz Osmałek
author_sort Piotr Gadziński
collection DOAJ
description <b>Introduction:</b> Many orally administered drugs are either unstable in the acidic environment of the stomach or cause moderate to severe side effects in the upper gastrointestinal tract (GIT). These limitations can reduce therapeutic efficacy, discourage patient compliance, worsen the disease, and even contribute to the risk of cancer development. To overcome these issues, drug release often needs to be modified and targeted to the distal parts of the GIT. This is typically achieved through the use of pH-sensitive polymer coatings or incorporation into polymeric delivery systems. With this in mind, the aim of this project was to design, develop, and characterize gellan gum-based beads for colon-specific prolonged release of mesalazine, with potential application in the chemoprevention and treatment of bowel diseases. <b>Materials and Methods:</b> The dehydrated capsules were characterized using Raman spectroscopy and scanning electron microscopy. The crosslinked gellan gum was additionally evaluated for cytotoxicity. Key parameters such as pH-dependent swelling behavior, drug content, encapsulation efficiency, and drug release in simulated gastrointestinal fluids were also assessed. Furthermore, the behavior of the capsules in the gastrointestinal tract was studied in a rat model to evaluate their in vivo performance. <b>Results:</b> Significant differences in drug release profiles were observed between formulations crosslinked solely with calcium ions and those additionally crosslinked with glutaraldehyde (GA). The incorporation of GA effectively prolonged the release of mesalazine. These findings were further supported by in vivo studies conducted on Wistar rats, where the GA-crosslinked formulation demonstrated a markedly extended release compared to the formulation prepared using only ionotropic gelation. <b>Conclusions:</b> The combination of ionotropic gelation and glutaraldehyde crosslinking in gellan gum-based beads appears to be a promising strategy for achieving colon-specific prolonged release of mesalazine, facilitating targeted delivery to the distal regions of the gastrointestinal tract.
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spelling doaj-art-184cd9f3bb6c446cbc90867a656cfd762025-08-20T01:56:39ZengMDPI AGPharmaceutics1999-49232025-04-0117556910.3390/pharmaceutics17050569Ionotropic Gelation and Chemical Crosslinking as Tools to Obtain Gellan Gum-Based Beads with MesalazinePiotr Gadziński0Agnieszka Skotnicka1Natalia Lisiak2Ewa Totoń3Błażej Rubiś4Ewa Florek5Dariusz T. Mlynarczyk6Mirosław Szybowicz7Ewelina Nowak8Tomasz Osmałek9Chair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Poznań, PolandChair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Poznań, PolandDepartment of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Poznan, PolandDepartment of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Poznan, PolandDepartment of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Poznan, PolandLaboratory of Environmental Research, Department of Toxicology, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Poznań, PolandChair and Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, PolandInstitute of Materials Research and Quantum Engineering, Faculty of Materials Engineering and Technical Physics, Poznań University of Technology, Piotrowo 3, 60-965 Poznań, PolandInstitute of Materials Research and Quantum Engineering, Faculty of Materials Engineering and Technical Physics, Poznań University of Technology, Piotrowo 3, 60-965 Poznań, PolandChair and Department of Pharmaceutical Technology, Poznan University of Medical Sciences, 3 Rokietnicka Street, 60-806 Poznań, Poland<b>Introduction:</b> Many orally administered drugs are either unstable in the acidic environment of the stomach or cause moderate to severe side effects in the upper gastrointestinal tract (GIT). These limitations can reduce therapeutic efficacy, discourage patient compliance, worsen the disease, and even contribute to the risk of cancer development. To overcome these issues, drug release often needs to be modified and targeted to the distal parts of the GIT. This is typically achieved through the use of pH-sensitive polymer coatings or incorporation into polymeric delivery systems. With this in mind, the aim of this project was to design, develop, and characterize gellan gum-based beads for colon-specific prolonged release of mesalazine, with potential application in the chemoprevention and treatment of bowel diseases. <b>Materials and Methods:</b> The dehydrated capsules were characterized using Raman spectroscopy and scanning electron microscopy. The crosslinked gellan gum was additionally evaluated for cytotoxicity. Key parameters such as pH-dependent swelling behavior, drug content, encapsulation efficiency, and drug release in simulated gastrointestinal fluids were also assessed. Furthermore, the behavior of the capsules in the gastrointestinal tract was studied in a rat model to evaluate their in vivo performance. <b>Results:</b> Significant differences in drug release profiles were observed between formulations crosslinked solely with calcium ions and those additionally crosslinked with glutaraldehyde (GA). The incorporation of GA effectively prolonged the release of mesalazine. These findings were further supported by in vivo studies conducted on Wistar rats, where the GA-crosslinked formulation demonstrated a markedly extended release compared to the formulation prepared using only ionotropic gelation. <b>Conclusions:</b> The combination of ionotropic gelation and glutaraldehyde crosslinking in gellan gum-based beads appears to be a promising strategy for achieving colon-specific prolonged release of mesalazine, facilitating targeted delivery to the distal regions of the gastrointestinal tract.https://www.mdpi.com/1999-4923/17/5/569gellan gumionotropic gelationmodified releasebioavailabilitydrug delivery
spellingShingle Piotr Gadziński
Agnieszka Skotnicka
Natalia Lisiak
Ewa Totoń
Błażej Rubiś
Ewa Florek
Dariusz T. Mlynarczyk
Mirosław Szybowicz
Ewelina Nowak
Tomasz Osmałek
Ionotropic Gelation and Chemical Crosslinking as Tools to Obtain Gellan Gum-Based Beads with Mesalazine
Pharmaceutics
gellan gum
ionotropic gelation
modified release
bioavailability
drug delivery
title Ionotropic Gelation and Chemical Crosslinking as Tools to Obtain Gellan Gum-Based Beads with Mesalazine
title_full Ionotropic Gelation and Chemical Crosslinking as Tools to Obtain Gellan Gum-Based Beads with Mesalazine
title_fullStr Ionotropic Gelation and Chemical Crosslinking as Tools to Obtain Gellan Gum-Based Beads with Mesalazine
title_full_unstemmed Ionotropic Gelation and Chemical Crosslinking as Tools to Obtain Gellan Gum-Based Beads with Mesalazine
title_short Ionotropic Gelation and Chemical Crosslinking as Tools to Obtain Gellan Gum-Based Beads with Mesalazine
title_sort ionotropic gelation and chemical crosslinking as tools to obtain gellan gum based beads with mesalazine
topic gellan gum
ionotropic gelation
modified release
bioavailability
drug delivery
url https://www.mdpi.com/1999-4923/17/5/569
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