Formulation parameters of fluoroquinolone-loaded liposomes and in vitro antimicrobial activity

Abstract

To load pefloxacin and ofloxacin in liposomes, two preparation procedures were carried out, leading to the formation of multilamellar vesicles (MLVs) or reverse-phase evaporation vesicles (REVs). MLVs were able to entrap greater amounts of the two drugs than REVs, especially when the drugs were co-dissolved with the lipid mixture in the organic phase. The encapsulation efficiency was influenced by the presence of a negatively charged lipid in the liposome composition: the greater the content of charged lipidic compound, the larger is the amount of drug entrapped. Among the charged systems, a dipalmitoylphosphatidylcholine-cholesterol-dihexadecyl phosphate mixture (4:3:4 molar ratio) showed the highest trapping capacity. The fluidity of the bilayer could also influence the encapsulation efficiency. In fact, the increase in encapsulation capacity for the lecithin-cholesterol-dihexadecyl phosphate mixture (4:3:4 molar ratio) conformed to the following order: dipalmitoylphosphatidylcholine > dimyristoylphosphatidylcholine > egg phosphatidylcholine. Variation in pH values led to different encapsulation efficiency and release rate. In vitro experiments on the antimicrobial activity of the encapsulated fluroquinolones compared to the free drug demonstrated a reduction of at least 50% of the minimal inhibitory concentration.