Preliminary study on the application of guar gum-based hydrogel in sepsis therapy

The oxidized guar gum-based hydrogel crosslinked with gelatin (OxGG:Gel), presenting antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), high cell viability and non-irritating nature, was evaluated in the rat experimental model of sepsis. Sepsis was induced by cecal ligation and puncture (CLP) and the controls (SHAM) underwent a laparotomy and cecal exposure. After 6 h, CLP and SHAM received the precursor solution mixture of OxGG:Gel (OxGG and gelatin) at 2% concentration in single dose (20 mg/kg; i.p.) or daily at 5% concentration (50 mg/kg; p.o.) for 5 days. Clinical signs and survival rate were analyzed before and after induction. The treatment of the CLP group with 2% solution (20 mg/kg i.p.) reduced signs of prostration and piloerection and was protective in parameters of temperature and glycemia compared to CLP. However, the per oral application of a 5% concentrated solution (50 mg/kg), not only lacked effect but also seemed to induce side effects (blindness, suffocation, and increased respiratory rate). In conclusion, OxGG:Gel administered in septic rats by intraperitoneal route at 20 mg/kg, but not per oral at 50 mg/kg, reduced signs of prostration and piloerection and showed a protective effect on temperature and glycemia. The adhesion of the viscous 5% solution to the mucosa, and rapid gelation may obstruct the airways, leading to respiratory distress and subsequent animal death. Since these adverse effects appeared in both SHAM and CLP groups, they can be assigned to the administration route rather than the hydrogel's chemical or biological properties. The administration route and concentration modulate the therapeutic efficacy of hydrogels for sepsis management.