Hydrophobic ion pairing for sustained local delivery of vancomycin from biodegradable nanospheres

We have demonstrated the efficacy of a novel strategy for achieving the prolonged and sustained release of vancomycin as a prophylaxis against surgical site infection (SSI). This strategy uses hydrophobic ion pairing (HIP), joining vancomycin with counter ions and efficiently encapsulating the antibiotic in biodegradable polymer nanospheres. To complete the process, vancomycin-complexes were formed in an aqueous acidic medium, and then they were encapsulated in poly(lactic-co-glycolic) acid (PLGA), polylactic acid (PLA), and polycaprolactone (PCL) nanospheres via the double-emulsion solvent-evaporation method. Our results show that sulfate and sulfonate-based counter ions provide the most effective structure for vancomycin-HIP formation, achieving 95% complexation efficiency at a 1:2 molar ratio. Once formed, the vancomycin-dioctyl sodium sulfosuccinate (Van-DOSS) complex achieved a 3.7-fold increase in lipophilicity (LogP _{octanol/water}), which significantly improved encapsulation efficiency in comparison to unmodified vancomycin. Encapsulation efficiency increased by 2.7-fold in PLGA (64.7% ± 0.4%) and by 5.5-fold in PLA (46.7 ± 5.9%) and PCL (47.7 ± 6.9%). The Van-HIP nanospheres achieved an in-vitro release of vancomycin that was three-to-five times the minimum inhibitory concentration required for S. aureus over the critical 28-day window indicated for post-operative care after spine surgery. Consequently, these findings support a sustained-release option for antibiotic formulation to improve surgical outcomes.