LHRH固体脂质纳米粒口服给药系统的研究

Study on LHRH-loaded solid lipid nanoparticles for oral administration

目的考察以固体脂质纳米粒为载体包裹促黄体生成素释放激素的类似物(LHRH-A2)口服给药的可行性。方法采用溶剂扩散法制备LHRH-A2单硬脂酸甘油酯纳米粒(LHRH—A2 loaded monostearin solid lipid nanoparticles,LHRH-A2-MSLN),考察载药纳米粒的粒径、Zeta电位等理化性质;用HPLC测定药物的包封率及体外释放特性;以花(鱼骨)鱼(Hemibarbus maculates Bleeker)为模型动物,载药纳米粒经口灌给药后,分别测定鱼的受精率和催产率。结果LHRH-A2-MSLN的粒径为(284.1±103.6)nm,纳米粒Zeta电位为-(19.4±1.1)mV,HPLC测得药物包封率为63.4%。体外释放研究结果显示,LHRH-A2-MSLN在前8 h快速释放了纳米粒所载药物的26.8%,随后每天以1.9%的速率持续释放。体内药效学研究表明,50μg·kg-1剂量的LHRH-A2-MSLN 口灌给药后,平均催产率46.5%,受精率90.5%。结论用溶剂扩散法制备得到的LHRH-A2-MSLN具有一定的口服有效性。

OBJECTIVE To evaluate the feasibility of LHRH-A2-loaded monostearin solid lipid nanoparticles （LHRH-A2-MSLN） as a novel preparation for oral administration.METHODS LHRH-A2-MSLN was prepared by a solvent diffusion method in aqueous system. The size, Zeta potential （charge）, entrapment efficiency of drug-loaded nanoparticles, and drug release characterization were investigated. The induced ovulation rate and fertilization rate after an oral administration of LHRH-A2-MSLN to Hemibarbus maculatus Bleeker were determined.RESULTS The average diameter and Zeta potential of LHRH-A2-MSLN were 284.1nm and - 19.4 mV, respectively. About 63.4% LHRH-A2 were incorporated in MSLN. The drug-release behavior from MSLN suspension in vitro exhibited a biphasic pattern with a burst drug-release at the first 8 h at a percentage of 26.8% of loaded LHRH-A2 and a distinctly prolonged release over a monitored period of 3 d at the release rate of 1.9% of drug in each day. After the oral administration of LHRH-A2-MSLN （50μg·kg^-1 ）, the mean induced ovulation rate and fertilization rate of Hemibarbus maculatus Bleeker were 46.5 % and 90.5 %, respectivdy. CONCLUSION The results indicate that this LHRH-A2-MSLN prepared by solvent diffusion method demonstrated significant effectiveness on fish by an oral administration.