Chen Gang, Hou Shi-Xiang, Hu Ping, Hu Qiao-Hong, Guo Dan-Dan, Xiao Yu
Department of Pharmaceutical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2008 Jun;28(6):1022-4.
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.
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 determining 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.
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 of DA-loaded SLN, which also resulted in increased t(1/2) and mean residence time (MRT) by 0.5 and 1.9 folds respectively.
Nanoparticles can be a promising tympanic drug delivery system for topical drug administration in the treatment of inner ear diseases.
研究使用固体脂质纳米粒（SLN）将药物局部递送至内耳的可行性，并根据所递送药物在内耳中的药代动力学评估其治疗内耳疾病的潜力。
以Compritol 888 ATO为基质，采用热分散-超声技术制备载醋酸地塞米松（DA）的SLN。建立高效液相色谱法（HPLC）测定DA和地塞米松（Dex）。评估载DA的SLN的药物性质，包括粒径、包封率和体外释放情况。将载DA的SLN通过鼓室内注射或静脉注射给予豚鼠，用HPLC测定外淋巴液中Dex的浓度，以估算药代动力学参数。
载DA的SLN平均直径为106.8 nm，包封率为83.8%，纳米粒中DA的体外释放很好地符合威布尔分布，DA从SLN的缓释超过6天。豚鼠静脉注射载DA的SLN后，在外淋巴液中未检测到Dex。与鼓室内注射载Dex原位凝胶相比，鼓室内注射载DA的SLN后，外淋巴液中Dex的相对生物利用度为504%，同时t(1/2)和平均驻留时间（MRT）分别增加了0.5倍和1.9倍。
纳米粒可成为一种有前景的鼓室给药系统，用于内耳疾病的局部药物治疗。
