1. School of Pharmacy, Faculty of Medical Sciences, University of the West
Indies, Faculty of Medical Sciences, St Augustine, Trinidad & Tobago.
3. College of Pharmacy, Sullivan University, Louisville, KY 40205, USA.
Background: Recent findings suggest bacteria's ability to adapt to various classes of antibiotics through three distinct resistance mechanisms: lipopolysaccharide modification, increased drug efflux, and reduced porin pathway. These mechanisms involve the adaptive response by bacteria to specific signal due to antibacterial presence in its environment, leading to up- and down regulation of the efflux system (MexXY/OprM), and the porin pathway (OprD) respectively. Molecular encapsulation in niosomes could block signal generation and prevent bacteria from recognizing the presence of encapsulated drug molecules, enhance fusogenic properties and enable drug assimilation.
Methods: Niosomes of select fluoroquinolones (i.e. ciprofloxacin, gatifloxacin, levofloxacin and norfloxacin) were prepared using thin film rehydration method and the parameters controlling niosomal drug loading were investigated including the speed of evaporation, temperature of rehydration, time of rehydration and volume of rehydration, using percent (%) drug loading as output variable. In vitro activity of noisome encapsulated fluoroquinolones against twenty ciprofloxacinresistant bacteria strains (each of Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus) was determined by broth microdilution technique. Paired sample t-test was performed for independent sample comparison while multi-group analysis was done with one-way analysis of variance (ANOVA) and significance determined at 95 % confidence level using MINITAB 16 statistical package.
Results: Entrapment efficiencies for the fluoroquinolones were 71.11±1.39% (ciprofloxacin), 19.11±1.86% (gatifloxacin), 34.23±1.86% (levofloxacin) and 70.09±1.64% (norfloxacin) respectively. The formulations displayed temperature-dependent stability with the highest stability occurring at 5ºC and the lowest at 37ºC respectively. Drug diffusion across dialyzing membrane was slower from the vesicles and followed a more sustained profile compared with the non-encapsulated drug particles. Analysis of drug liberation kinetics suggests first-order (concentration-dependent) release from the vesicles.
Conclusions: The niosomes of fluoroquinolones produced at least two-fold reduction in MIC's against Pseudomonas aeruginosa and Escherichia coli, and at least four-fold reduction in MIC's against Staphylococcus aureus. Results therefore suggest the potential for enhancement of fluoroquinolones delivery to their target sites in the bacteria cytoplasm through formulation in niosomes.
Key words: fluoroquinolones, niosomes, drug delivery, in vitro antibacterial activity.