Prolonged local retention of vancomycin achieved by a multivesicular liposomes in thermoresponsive gel system for the prevention and treatment of intervertebral disc infection

Abstract

The therapeutic efficacy of intervertebral disc (IVD) infections treated with intravenous vancomycin (VCM) is often limited by inadequate blood supply to the IVD. In this study, we developed a localized and sustained-release drug delivery system for the intradiscal administration of VCM. First, VCM-loaded multivesicular liposomes (VCM-MVLs) were prepared using a two-step emulsification process, and we investigated the effects of the preparation process and formulation composition on the quality of the MVLs. The prepared MVLs exhibited an encapsulation efficiency of 92.08 ± 6.44 %, a particle size of 30.35 μm, and a sustained release over 12 days. Subsequently, VCM-MVLs were incorporated with PLGA-PEG-PLGA (PPP) to create a thermosensitive hydrogel composite formulation (VCM-MVL-PPP), which demonstrated a gelling temperature of 28.4°C and exhibited prolonged sustained release over 20 days. The antimicrobial activity of VCM-MVL-PPP was maintained for an extended duration of 21 days. Additionally, the VCM-MVL-PPP demonstrated an optimal retention capacity of 14 days in the in vivo retention assay. In vivo safety results confirmed the high biocompatibility and negligible toxicity of the formulation. In conclusion, the presence of PPP as a secondary release barrier for the drug released from MVLs allowed VCM-MVL-PPP to exhibit prolonged drug release and retention in the IVDs compared to VCM-MVLs. Our findings provide a valuable reference for peptide delivery and the treatment of disc infections.