吸入二丙酸倍氯米松纳米微囊的肺内分布及血药浓度测定

Pulmonary distribution of beclomethasone dipropionate nanocapsule in guinea pigs after spray inhalation

目的 :了解二丙酸倍氯米松聚乳酸聚乙醇酸 (BDP PL GA)纳米微囊体内分布和释药情况。方法 :豚鼠雾化吸入荧光素钠标记的 BDP纳米微囊 ,10分钟后观察其在肺组织中的分布。给豚鼠气管插管后、用喷雾法给予 BDP纳米微囊及普通制剂悬液 ,不同时间点取血及肺组织 ,用高压液相色谱法测定血浆及肺组织匀浆BDP浓度。结果 :雾化吸入 BDP纳米微囊后能较快进入肺泡组织。肺组织匀浆中 ,BDP普通制剂组 BDP峰浓度出现在 8小时左右 ,然后较快下降 ;BDP纳米微囊组释药呈双相动力学过程 :给药后 0 .5～ 1.0小时有一个相对的爆破释放 ,8小时左右达峰浓度 ,12小时开始 BDP浓度明显高于普通制剂组 ,并维持相当高浓度的平台期至 72小时。血浆中普通制剂组和纳米微囊组 BDP浓度均未测出。结论 :吸入给药后 ,肺组织中 BDP纳米微囊制剂能进入肺泡组织 ,并具有良好的缓释性且局部药物浓度明显高于血浆 。

Objective:To investigate the kinetics and distribution of beclomethasone dipropionate(BDP) nanocapsule in vivo.Methods:The pulmonary distribution was observed after spray inhalation of sodium fluoresencelabelled BDPpolydllactidecoglycolide acid(PLGA) nanocapsules at 10 minutes.Healthy guinea pigs were spray inhaled BDP PLGA nanocapsules after intratracheal intubation.BDP concentrations were detected at different time points in both plasma and lung tissue homogenates by high press liquid chromatography (HPLC).Results: Spray inhaled BDP nanocapsule was distributed hemogeneously.In lung tissue homogenates,the peak concentration of BDP was present at about 8 hours and then descended rapidly.In contrast,the release of BDP of BDP PLGA nanocapsules in vivo revealed biphasic kinetics,showing relatively rapid burstrelease at 0.51.0 hour, peaking at about 8 hours,followed by a high plateau of slowrelease up to 72 hours.However,BDP concentrations of both conventional preparation and BDPPLGA nanocapsules were not detected in plasma. Conclusions: BDP PLGA nanocapsules may be suitable for longterm inhaled therapy because of the good controlled release and lower concentrations of BDP in plasma.