Injectable hybrid delivery system composed of gellan gum, nanoparticles and gentamicin for the localized treatment of bone infections

<p>Objectives: Bone infections are treated with antibiotics administered intravenously, antibiotic-releasing bone cements or collagen sponges placed directly in the infected area. These approaches render limited effectiveness due to the lack of site specificity and invasiveness of implanting cements and sponges. To address these limitations, we developed a novel polysaccharide hydrogel-based injectable system that enables controlled delivery of gentamicin (GENT). Its advantages are minimal invasiveness, and localized and finely regulated release of the drug. Methods: GENT was incorporated both directly within the gellan gum hydrogel and into poly(L-lactide-co-glycolide) nanoparticles embedded into the hydrogel. Results: We confirmed the injectability of the system and measured extrusion force was 15.6 ± 1.0 N, which is suitable for injections. The system set properly after the injection as shown by rheological measurements. Desired burst release of the drug was observed within the first 12 h and the dose reached ~27% of total GENT. Subsequently, GENT was released gradually and sustainably: ~60% of initial dose within 90 days. In vitro studies confirmed antimicrobial activity of the system against Staphylococcus spp. and cytocompatibility with osteoblast-like cells. Conclusions: Developed injectable system enables minimally invasive, local and sustained delivery of the pharmaceutically relevant doses of GENT to combat bone infections.