Hydrogels are a cornerstone in drug delivery systems, valued for their ability to encapsulate and release therapeutic agents in a controlled manner. Their biocompatibility and tunable mechanical properties make them highly suitable for biomedical applications. While synthetic hydrogels have been widely studied, there is growing interest in natural polysaccharide-based hydrogels due to their eco-friendliness, biodegradability, and reduced immunogenicity. Injectable hydrogels, in particular, provide a minimally invasive platform for localized and sustained therapeutic delivery, reducing systemic side effects and improving patient compliance. This study focuses on the development of an innovative injectable hydrogel derived from natural polysaccharides, including Carrageenans, Tamarind Seed Polysaccharide (TSP), Xanthan gum, Gellan gum, and Locust Bean Gum (LBG). The hydrogel was designed to address challenges in protein delivery, such as uncontrolled diffusion and limited activity duration. Aqueous dispersions of each polysaccharide were thoroughly characterized for their rheological and mechanical properties, and specific associations were formulated to enhance the hydrogel’s performance. Two formulations, Hydrogel A and Hydrogel B, were developed, with Hydrogel A demonstrating superior rheological properties, structural recovery after mechanical stress, and biocompatibility, making it the optimal candidate. Release studies performed on Hydrogel A loaded with different proteins showed a significantly prolonged and controlled release profile, over extended period, while preserving the structural and functional integrity of the encapsulated protein. These results were mirrored by in vivo experiments, which assessed the biocompatibility and absence of side effects upon local subcutaneous injection of Hydrogel A while confirming the sustained release of a model therapeutic protein. In conclusion, this study presents an innovative polysaccharide-based injectable hydrogel as a promising platform for protein therapeutics. Combining biocompatibility, biodegradability, and controlled release properties, this hydrogel provides an effective and sustainable solution to improve the current challenges associated to in vivo protein delivery in pharmaceutical applications.

Innovative hydrogel formulation based on polysaccharides derived from natural sources for protein delivery

SCHIAVONE, GIORGIA
2025

Abstract

Hydrogels are a cornerstone in drug delivery systems, valued for their ability to encapsulate and release therapeutic agents in a controlled manner. Their biocompatibility and tunable mechanical properties make them highly suitable for biomedical applications. While synthetic hydrogels have been widely studied, there is growing interest in natural polysaccharide-based hydrogels due to their eco-friendliness, biodegradability, and reduced immunogenicity. Injectable hydrogels, in particular, provide a minimally invasive platform for localized and sustained therapeutic delivery, reducing systemic side effects and improving patient compliance. This study focuses on the development of an innovative injectable hydrogel derived from natural polysaccharides, including Carrageenans, Tamarind Seed Polysaccharide (TSP), Xanthan gum, Gellan gum, and Locust Bean Gum (LBG). The hydrogel was designed to address challenges in protein delivery, such as uncontrolled diffusion and limited activity duration. Aqueous dispersions of each polysaccharide were thoroughly characterized for their rheological and mechanical properties, and specific associations were formulated to enhance the hydrogel’s performance. Two formulations, Hydrogel A and Hydrogel B, were developed, with Hydrogel A demonstrating superior rheological properties, structural recovery after mechanical stress, and biocompatibility, making it the optimal candidate. Release studies performed on Hydrogel A loaded with different proteins showed a significantly prolonged and controlled release profile, over extended period, while preserving the structural and functional integrity of the encapsulated protein. These results were mirrored by in vivo experiments, which assessed the biocompatibility and absence of side effects upon local subcutaneous injection of Hydrogel A while confirming the sustained release of a model therapeutic protein. In conclusion, this study presents an innovative polysaccharide-based injectable hydrogel as a promising platform for protein therapeutics. Combining biocompatibility, biodegradability, and controlled release properties, this hydrogel provides an effective and sustainable solution to improve the current challenges associated to in vivo protein delivery in pharmaceutical applications.
15-apr-2025
Inglese
PIRAZZINI, MARCO
Università degli studi di Padova
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.14242/217602
Il codice NBN di questa tesi è URN:NBN:IT:UNIPD-217602