地塞米松纳米粒的体外释放及经圆窗给药在内耳的药代动力学研究  

In vitro dexamethasone release from nanoparticles and its pharmacokinetics in the inner ear after administration of the drug-loaded nanoparticles via the round window

作　　者：陈钢[1] 侯世祥[2] 胡平[3] 胡巧红[1] 郭丹丹[2] 肖宇[2] 

机构地区：[1]广东药学院药剂学教研室,广东广州510006 [2]四川大学华西药学院,四川成都610041 [3]香港浸会大学中医药学院,中国香港

出　　处：《南方医科大学学报》2008年第6期1022-1024,1027,共4页Journal of Southern Medical University

基　　金：广东省自然科学基金(07301575)~~

摘　　要：目的探求固体脂质纳米粒(SLN)作为内耳局部给药载体的可行性,为其治疗内耳疾病提供依据。方法采用热融-超声法以山榆酸甘油酯为载体材料制备醋酸地塞米松(DA)固体脂质纳米粒。建立DA和地塞米松(Dex)的高效液相色谱(HPLC)测定方法。测定DA-SLN的粒径和包封率,并考察其体外释放规律。经静脉和鼓室注射DA-SLN,测定药物在内耳外淋巴液(PL)的药动学参数。结果制备的DA-SLN平均粒径为106.8nm,包封率为83.8%。DA-SLN体外释放符合Weibull方程,释放时间可达6d以上。静脉注射DA-SLN后在PL中测不到药物。与鼓室注射地塞米松原位凝胶相比,鼓室注射DA-SLN在内耳Dex的相对生物利用度为504%,且MRT和t1/2分别是其2.9和1.5倍。结论纳米粒传递系统有望成为一种新型的治疗内耳疾病的鼓室给药载体,值得进一步研究。Objective To investigate the feasibility of local drug delivery into the inner ear using solid lipid nanoparticles （SLN） and evaluate its potential for inner ear disease treatment in terms of the pharmacokinetics of the delivered drug in the inner ear. Methods Dexamethasone acetate （DA）-loaded SLN was prepared with Compritol 888 ATO as the matrix by means of hot dispersion-ultrasonic technique. A high-performance liquid chromatography （HPLC） was established for determing DA and dexamethasone （Dex）. The pharmaceutical properties of DA-loaded SLN including the particle size, entrapment ratio and in vitro release were estimated. DA-loaded SLN was administered via intratympanic injection or intravenous injection in guinea pigs and Dex concentration in the perilymph was measured with HPLC for estimation of the pharmacokinetic parameters. Results The mean diameter of the DA-loaded SLN was 106.8 nm with entrapment ratio of 83.8%, and the in vitro DA release from the nanoparticles well conformed to Weibull distribution, with sustained-release of DA from the SLN exceeding 6 days. After intravenous injection of DA-loaded SLN in guinea pigs, Dex failed to be detected in the perilymph. Compared with Dex-loaded in situ gel following intratympanic injection, the relative bioavailability of Dex in the perilymph was 504% following intratympanic injection ofDA-loaded SLN, which also resulted in increased t1/2 and mean residence time （MRT） by 0.5 and 1.9 folds respectiuely. Conclusion Nanoparicles can be a promising tympanic drug delivery system for topical drug administration in the treatment of inner ear diseases.

关 键 词：固体脂质纳米粒 地塞米松 鼓室给药 山榆酸甘油酯 耳聋 

分 类 号：R96[医药卫生—药理学]