Ciprofloxacin surf-plexes in sub-micron emulsions: A novel approach to improve payload efficiency and antimicrobial efficacy

The aim of this study was to investigate antimicrobial efficacy and pharmacokinetic profile of ciprofloxacin (CFn) loaded oil-in-water (o/w) submicron emulsion (SE-CFn). This study emphasized on development of hydrophobic ion-pair complexes of CFn with sodium deoxycholate (SDC) [CFn–SDC], which was incorporated in the core of SE (SE-CFn–SDC). SE-CFn–SDC was characterized for globulet size (278 ± 12 nm), zeta potential (−25.3 ± 1 mV), viscosity (2.6 ± 0.3 cP), transmission electron microscopy (TEM), drug entrapment and for in vitro release profile. The entrapment efficiency (EE) was significantly improved (≥80%; p ≤ 0.05) on ion-pairing while it was merely 27.2 ± 3.1% for free CFn. The cytotoxicity studies of formulations on J774 macrophage cells showed that more than 90 ± 3% of cells were viable, even at high concentration (100 μg/ml). SE-CFn–SDC was further modified with cationic inducer chitosan (SE-CH–CFn–SDC), which showed almost twofold and fourfold enhancement in antimicrobial efficacy as compared to SE-CFn-SDC and SE-CFn, respectively when tested in vitro against E. coli, S. aureus, and P. aeruginosa. When tested in male Balb/c mice, the AUC0–24 h of SE-CH–CFn–SDC (23.27 ± 2.8 h μg/ml) was found to be 1.7-fold and 5-fold higher as compared to SE-CFn-SDC (13.17 ± 0.88 h μg/ml) and CFn solution (4.70 ± 0.77 h μg/ml), respectively. The study demonstrates that surfactant based ionic complex formation incorporated in surface modified submicron emulsion is a promising approach to improve payload efficiency of poorly water soluble drugs with improved antimicrobial efficacy and pharmacokinetic profile.

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