鼻用佐米曲普坦脂质体原位凝胶剂的脑靶向性及药动学的初步评价

Preliminary evaluation of brain-targeting and pharmacokinetics of zolmitriptan liposome in situ nasal gel agent

目的制备鼻用佐米曲普坦脂质体原位凝胶剂,并探讨其经鼻给药的脑靶向性及药动学特征。方法采用薄膜超声分散法制备佐米曲普坦脂质体,去乙酰结冷胶进一步制备成原位凝胶制剂。雄性SD大鼠随机分为2组,分别经鼻腔给予佐米曲普坦脂质体原位凝胶剂及经尾静脉注射佐米曲普坦溶液,剂量均为0.5 mg·kg-1。采用高效液相色谱法测定给药后不同时间点血浆、脑匀浆样品中佐米曲普坦的含量。采用WinNonlin软件计算主要药动学参数及脑靶向指数。结果佐米曲普坦脂质体粒径在200 nm以下,分布较均匀,包封率大于80%。与佐米曲普坦溶液经静脉途径给药相比,原位凝胶剂经鼻给药后血浆及脑内佐米曲普坦的消除半衰期分别延长1.60及2.32倍,脑靶向指数达到10.53。结论鼻用佐米曲普坦脂质体原位凝胶剂具有长效特点,并能显著提高脑靶向性。

Objective To prepare zolmitriptan liposome in situ nasal gel agent, and to investigate its Brain Targeting and pharmacokinetic characteristics.Methods Zolmitriptan liposomes were prepared by ultrasonic dispersion with thin film, and further prepared into in-situ gel preparation using deacetylated gellan.Male SD rats were randomly divided into two groups and given zolmitriptan liposome in-situ gel agent via nasal cavity or zolmitriptan solution via tail vein at a dose of 0.5 mg·kg-1.High performance liquid chromatography(HPLC) was used to determine zolmitriptan in plasma and brain homogenate samples at different time points after administration.The main pharmacokinetic parameters and BTI(brain targeting index) were calculated by WinNonlin software.Results The particle size of zolmitriptan liposome was below 200 nm, the distribution was uniform, and the encapsulation efficiency was more than 80%.Compared with zolmitriptan solution administered intravenously, the elimination half-lifes(t1/2) of zolmitriptan in plasma and brain of in-situ gel agent were extended by 1.60 and 2.32 times, respectively, with BTI reaching 10.53.Conclusion Zolmitriptan liposome in situ nasal gel agent has the characteristics of long-term effect and can significantly improve brain targeting.