INTRAVITREAL PHARMACOKINETICS OF LIPOSOME-ENCAPSULATED AMIKACIN IN A RABBIT MODEL

Background. Intravitreal injection of antibiotics has become a standard therapy for bacterial endophthalmitis. The duration of effective antimicrobial levels in the vitreous after single injection, however, may not be long enough to get optimal response. The authors prepared liposome-encapsulated amikacin for prolonging the duration of intravitreal therapeutic concentrations and investigated the intravitreal pharmacokinetics of the liposomes and amikacin in phosphate buffer solution (PBS) as control. Methods: The liposome-encapsulated amikacin was prepared by reverse-phase evaporation method. The intravitreal pharmacokinetics of the liposomes was compared with amikacin in PBS by fluorescence polarization immunoassay. Albino rabbits were randomly distributed into 12 groups. Rabbits in groups 1 to 6 and in groups I to VI (control groups) received an intravitreal injection of the liposome-encapsulated amikacin and amikacin in PBS, respectively. Results: The encapsulation rate of amikacin was 91%. The time of 50% spontaneous degradation (half-life) of the liposomes in PBS (38-degrees-C, pH 7.4) was 47.6 days, and the time of 50% release (half-life) of the drug from the liposomes in PBS was 84.8 hours. The vitreous amikacin concentrations in groups 1 to 6 were significantly greater (P < 0.05) than those in control groups I to VI in every time interval, except in groups 1 to 3 at 1 hour after injection. The difference was particularly obvious in the endophthalmitis groups. The clearance of encapsulated amikacin in vitreous appeared to be related to the state of blood-ocular barrier and to the structural integrity of vitreous. The distribution, the absorption, and the elimination of encapsulated amikacin in vitreous showed the first-order kinetics. Conclusion: The liposome-encapsulated amikacin prolonged half-life of the drug in vitreous. The results of the pharmacokinetic analysis suggested that in endophthalmitis, especially in severe cases, the liposomes may be preferable to conventional preparation.