Assessment of solution stability and drug release properties of liposomal curcumin in peritoneal dialysis fluid and its synergistic antibacterial activity with vancomycin

Abstract

Infectious Peritonitis associated with recurrent and persistent infections is the major cause of technique failure of life-sustaining peritoneal dialysis (PD) therapy used for treating patients with end-stage renal failure (ESRF). The infections -if diagnosed timely- are usually resolved with empiric antibiotic treatment. However, the treatment of infections associated with drug resistant bacteria or fungal infections remains challenging, poses a very serious problem to the health of PD patients, and is the leading cause of mortality and morbidity. Therefore, the development of alternate approaches other than antibiotics are required to keep up with the constantly changing and increasing multiple drug resistance (MDR) of bacterial strains. Curcumin exhibits anti-oxidative/anti-inflammatory potential and remarkable wound healing properties. It also has broad-spectrum anti-bacterial/anti-biofilm effects and its synergistic antibacterial activity with several antibiotics (including those used clinically for the treatment of PD associated infections) is well proven against variety of pathogenic infections including MDR strains. However, poor water-solubility of curcumin (<0.125 mg/L) remains a major barrier to achieve desirable bioavailability and further limit its therapeutic efficacy. Among the various drug carrier strategies, liposomal encapsulation has been found to be most promising mode to remarkably enhance the therapeutic index of curcumin by facilitating its gastric absorption, protecting its enzymatic degradation and allowing its slow release over time for maximum benefits. However, to date, the potential of liposomal curcumin has not been explored for the treatment of PD associated infections. Starting our efforts in this direction, a comprehensive assessment of solution stability and drug release properties of curcumin-loaded liposomal vesicles has been demonstrated in peritoneal dialysis fluid. The results clearly indicated an excellent solution stability of curcumin loaded inside liposome and the formulation affirms the regulated curcumin release enhancing the bioavailability. Further, we evaluated the synergistic antibacterial efficacy of curcumin-loaded liposomal formulation with vancomycin against the Staphylococcus aureus and Escherichia coli – pathogens (known for causing intra-peritoneal infections during PD). This synergy strategy resulted in outstanding improvement in bacterial inhibition efficacy of liposomal curcumin at significantly lowered doses. The results of the present study propose lipocurcumin as a potent antibiotic additive to vancomycin to cure PD-infections caused by antibiotic-resistant bacteria.