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 mu g/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 AUC(0-24) (h) of SE-CH-CFn-SDC (23.27 +/- 2.8 h mu g/ml) was found to be 1.7-fold and 5-fold higher as compared to SE-CFn-SDC (13.17 +/- 0.88 h mu g/ml) and CFn solution (4.70 +/- 0.77 h mu g/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. (C) 2011 Elsevier B.V. All rights reserved.