Zeng S, Hu C, Wei H, Lu Y, Zhang Y, Yang J, Yun G, Zou W, Song B
Department of Ophthalmology, Union Hospital, Tongji Medical University, Wuhan, People's Republic of China.
Ophthalmology. 1993 Nov;100(11):1640-4. doi: 10.1016/s0161-6420(93)31423-5.
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.
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.
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.
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.
玻璃体内注射抗生素已成为细菌性眼内炎的标准治疗方法。然而，单次注射后玻璃体内有效抗菌水平的持续时间可能不够长，无法获得最佳反应。作者制备了脂质体包裹的阿米卡星，以延长玻璃体内治疗浓度的持续时间，并研究了脂质体和阿米卡星在磷酸盐缓冲溶液（PBS）中的玻璃体内药代动力学作为对照。
采用逆相蒸发法制备脂质体包裹的阿米卡星。通过荧光偏振免疫分析法比较脂质体与PBS中阿米卡星的玻璃体内药代动力学。白化兔随机分为12组。第1至6组和第Ⅰ至Ⅵ组（对照组）的兔子分别接受玻璃体内注射脂质体包裹的阿米卡星和PBS中的阿米卡星。
阿米卡星的包封率为91%。脂质体在PBS（38℃，pH 7.4）中的50%自发降解时间（半衰期）为47.6天，药物从脂质体在PBS中的50%释放时间（半衰期）为84.8小时。除注射后1小时的第1至3组外，第1至6组玻璃体内阿米卡星浓度在每个时间间隔均显著高于对照组Ⅰ至Ⅵ组（P<0.05）。在眼内炎组中差异尤为明显。玻璃体内包裹的阿米卡星清除率似乎与血眼屏障状态和玻璃体结构完整性有关。玻璃体内包裹的阿米卡星的分布、吸收和消除呈现一级动力学。
脂质体包裹的阿米卡星延长了药物在玻璃体内的半衰期。药代动力学分析结果表明，在眼内炎，尤其是严重病例中，脂质体可能比传统制剂更具优势。
