丙酸倍氯米松纳米微囊的肺内分布及清除的研究

A study on pharmacokinetics and pulmonary distribution and clearance of beclomethasone dipropionate nano-microcapsules

目的研究丙酸倍氯米松(BDP)纳米微囊的肺内分布及清除特征,探讨BDP纳米微囊的肺沉积及缓释作用。方法①采用W/O/W乳化法和蒸法去溶剂法,以聚乳酸-聚乙醇酸的共聚物(PLGA)为囊材,制备BDP-PLGA纳米微囊并用扫描电镜测粒径及观察表面特征。②豚鼠雾化吸入3H-BDP-PLGA纳米微囊,取肺组织切片,荧光显微镜下观察肺内分布。③56只昆明种小鼠随机分成2组(3H-BDP组和3H-BDP-PLGA纳米微囊组)。气管内给药后不同时间点取肺组织,通过液体闪烁计数器测放射性剂量。结果①BDP-PLGA纳米微囊呈表面光滑的球形,中位粒径220.4nm。豚鼠雾化吸入包有荧光素钠的纳米微囊后,下呼吸道末端及肺泡均可观察到沉积的荧光颗粒,并可维持数天。②肺内药物含量,给药后1、15min,BDP组与其PLGA纳米微囊组无统计学意义,随着时间的延长,BDP-PLGA纳米微囊组高于BDP组。结论①BDP-PLGA纳米微囊粒径小,雾化吸入后,在外周肺组织有广泛的沉积。②与原型药相比,BDP-PLGA纳米微囊在小鼠体内有良好的释药特征,随着囊壁的降解,逐步释放出药物。延长药物在肺内停留时间,在不增加剂量的情况下,更长时间发挥局部抗炎作用。

Objective To study the characteristics of pulmonary distribution and clearance of beclomethasone dipropionate （BDP） nano-microcapsule and its lung deposition and slow-releasing effects. Methods ①The BDP nano-microcapsules were prepared by using poly lactic-glycolic acid （PLGA） as matrix and the water-in-oil-in-water （W/O/W） emulsfication and solvent evaporation techniques. The morphology and diameter of nano-microcapsules were observed by scanning electron microscope.②The BDP-PLGA nano-microcapsules co-loaded with BDP and fluorescein sodium were nebulised to guinea pigs, and their tissue section of lung were prepared to observe the pulmonary distribution of BDP nano-microcapsules with fluorescence microscope. ③Fifty-six mice were randomly divided into two groups （^3H-BDP group and ^3H-BDP-PLGA nano-microcapsules group） ,their lung tissues were harvested at different time-point after drug administration intratracheally for assaying radioactivity through liquid scintillation counter. Results ①The features of BDP-PLGA nano-microcapsules were described as microspheres with smooth surface and average diameters 220.4 nm. Fluorescence granules had been observed in distal end of lower respiratory tract and alveoli of guinea pig for several days after inhaled nebulized nano-microcapsules encapsulated fluorescein sodium. ② There was no significant difference between the drug remaining in lungs of BDP and BDP-PLGA nano-microcapsules at 1 and 15 minutes ,and with time prolonging the drug remains in BDP-PLGA group was higher than that in BDP group. Conclusion ①The inhaled BDP-PLGA nano-microcapsules have a wide spread deposition in peripheral lung tissue for its micronized diameter. ② Compared with BDP, BDP-PLGA nano-microcapsules have good sustained release character in rnice ,encapsulated drug is slow releasing with nano-microcapsules degradation. It appears that the prolonged lung retention of BDP by using PLGA nanomicrocapsules could lead to prolong its anti-inflammation duration without increasing drug dosage.