[Clearance of liposome-incorporated ciprofloxacin after intravitreal injection in rabbit eyes]

Ciprofloxacin (CIP) is a fluoroquinolone-antibiotic with a high antimicrobial activity against all pathogens causing bacterial endophthalmitis. After intravitreal injection, however, elimination half-life of this antibiotic is only 2.2 hours. To prolong intraocular bioavailability this study was performed to incorporate CIP into liposomes and to determine its clearance from the vitreous after intravitreal injection.CIP was incorporated into multilamellar vesicles by mechanical dispersion. 0.1 ml of this suspension (equiv. 273.6 micrograms CIP) was injected into the midvitreous of pigmented rabbit eyes (Chinchilla-bastards). One day, 3 and 14 days after the injection intravitreal concentration of CIP was determined by means of high-pressure-liquid-chromatography after dissolution of the liposomes by ultrasound. At the same intervals serum concentration of the antibiotic was examined as well.Within 24 hours intravitreal concentration fell to 18.0 micrograms/ml. Three days after the injection the concentration of CIP was 6.9 micrograms/ml. This is still above the minimal inhibitory concentration (MIC90) of the most common ocular pathogens. At 14 days CIP was not detectable in the vitreous any more. The serum concentration was between 0.04 microgram/ml and 0.07 microgram/ml. 3 and 14 days after injection no CIP could be detected.This study shows that the incorporation of CIP into liposomes can be achieved in sufficient doses by mechanical dispersion method. After intravitreal application the bioavailability of the antibiotic can be markedly improved. Even after 3 days the intravitreal levels were above the MIC90 of the most common endophthalmitis pathogens.