Thermosensitive multivesicular liposomal hydrogel: a potential platform for loco-regional drug delivery in the treatment of osteomyelitis caused by antibiotic-resistant biofilm-forming bacteria.

Biofilm-mediated osteomyelitis presents significant therapeutic challenges. Given the limitations of existing osteomyelitis treatment approaches, there is a distinct need to develop a localized drug delivery system that is biocompatible, biodegradable, and capable of controlled antibiotic release. Multivesicular liposomes (MVLs), characterized by their non-concentric vesicular structure, distinct composition, and enhanced stability, serve as the system for a robust sustained-release drug delivery platform. In this study, various hydrogel formulations composed of poloxamer 407 and other hydrogels, incorporating vancomycin hydrochloride (VAN HL)-loaded MVLs (VAN HL-MVLs), were prepared and evaluated. The optimized VAN HL-MVL sol-gel system, consisting of poloxamer 407 and hyaluronic acid, successfully maintained drug release for up to 3 weeks and exhibited shear-thinning behavior at 37°C. While complete drug release from MVLs alone took place in 312 h, the hydrogel formulation extended this release to 504 h. The released drug effectively inhibited the Staphylococcus aureus biofilms growth within 24 h and methicillin-resistant S. aureus biofilms within 72 h. It also eradicated preformed biofilms of S. aureus and methicillin-resistant S. aureus in 96 and 120 h, respectively. This injectable in situ gel system incorporating VAN HL-MVLs holds potential as an alternative to undergoing multiple surgeries for osteomyelitis treatment and warrants further studies.