Daptomycin-loaded biodegradable thermosensitive hydrogels enhance drug stability and foster bactericidal activity against Staphylococcus aureus

A drug delivery system based on fully biodegradable thermosensitive hydrogels enabling controlled antibiotic release may support the management of implant-associated infections. In this work, the lipopeptide antibiotic daptomycin was encapsulated in hydrogel networks consisting of vinyl sulfonated triblock copolymers of PEG-p (HPMAm-lac(1,2)) and thiolated hyaluronic acid. High concentrations of active daptomycin exceeding the minimum biofilm eradicating concentration were sustainably eluted from the biodegradable carrier. The drug release profiles were tailored by varying the degree of substitution (DS) of thiol groups of hyaluronic acid, reaching a plateau level after 200 and 330 h for DS values of 53% and 31%, respectively. The hydrogel polymeric network preserved the structural stability of the loaded antibiotic and retained the calcium-dependent daptomycin activity, showing a noticeable biofilm bactericidal effect against a 24 h-old Staphylococcus aureus biofilm in vitro. The two-component thermosensitive hydrogels demonstrated to be an excellent antibiotic releasing scaffold with potential clinical applications in the management of implant-associated infections.