Nature-Derived Hydrogels as Sustainable Carriers for Controlled Protein Drug Delivery

Hydrogels are highly flexible matrixes with three-dimensional polymer networks able to absorb large amount of water. In drug delivery, they can be used as reservoir systems for the controlled release of encapsulated therapeutics. Injectable hydrogels, in particular, are endowed with notable effectiveness due to their biocompatibility and minimally invasive administration which enables localised and sustained delivery, while reducing systemic side effects. Interest in hydrogels formulated with natural polysaccharides has recently increased due to their favourable properties, such as eco-friendliness, biodegradability, and low immunogenicity. This study focuses on the development of an injectable hydrogel based on natural polysaccharides for the delivery of protein therapeutics. Rheological tests were performed to assess the viscoelastic parameters of different formulations and their consistency at various time points, confirming the hydrogel nature of the preparations over time and after the syringing process. SEM analyses were performed to monitor injection impact on the structure and microporosity, which resulted unaltered despite the mechanical stress applied by the syringing process. Additionally, in vitro tests were conducted to evaluate the hydrogel’s swelling capacity, which showed an initial swelling behavior followed by partial erosion of the system. Altogether, these physical and chemical characterizations indicated the suitability of this natural polysaccharides-based hydrogel as an injectable system for drug delivery purposes. In vitro studies with a model therapeutical protein were performed to characterize the release properties, which showed a controlled and prolonged release of the encapsulated protein compared to the protein formulated in the saline solution. In vivo experiments on a mouse model ascertained the biocompatibility and the lack of side effects of the hydrogel following its local subcutaneous injection and confirmed the progressive emptying of the loaded protein with limited systemic diffusion. In conclusion, this study presents an injectable polysaccharide-based hydrogel as an innovative protein delivery system due to its biocompatibility, biodegradability and controlled release profile. This could lead to a new formulation for protein local delivery with prolonged activity, minimising the risks of side effects associated with systemic diffusion.