Chitosan Hydrogels Enriched with Biocompounds Extracted from Marine Sponges: Potential to Modulate the Inflammatory Process in an In Vitro Study

Hydrogels are recognized as effective drug delivery systems in medical and pharmaceutical applications. Among them, chitosan (CH) hydrogels stand out for their biocompatibility, biodegradability, and ability to release bioactive substances. This is especially promising for anti-inflammatory compounds since inflammation is associated with various diseases. Although effective, conventional anti-inflammatory drugs, when administered orally and over the long term, can cause side effects, stimulating the search for natural alternatives and safer release systems. Furthermore, in the search for natural bioactives, it is known that a source of biocompounds that is still little explored, despite its potential, is the marine sponge Dysidea robusta. The aim of this study was to develop and characterize chitosan-based hydrogels enriched with biocompounds derived from the marine sponge Dysidea robusta. Four chitosan hydrogel formulations were synthesized using varying concentrations of urease and urea, and their physical and morphological properties were evaluated using the mass loss test and techniques such as Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and rheology. Seven biocompounds from the marine sponge Dysidea robusta (DR1 to DR7) were obtained and incorporated into a hydrogel formulation with optimal gelation time, stability, and presence of pores (H3). Drug release capacity was analyzed, as well as in vitro biological activity through viability and cell proliferation assays with fibroblasts and chondrocytes, along with immunoassays for pro-inflammatory cytokines IL-6 and TNF-α in macrophages. The results showed that all the hydrogels were stable and biocompatible, with H3 being selected due to its physical profile. Notably, the hydrogel enriched with the DR5 compound significantly reduced IL-6 levels and showed potential for controlled drug release over time. These findings highlight the promise of chitosan hydrogels as injectable carriers for natural anti-inflammatory compounds, suggesting their applicability in therapies for inflammatory diseases.