地塞米松磷酸钠脂质体壳聚糖胶囊的结肠定位释药与吸收研究

Study on the colon site-specific delivery of chitosan capsule filled with dexamethasone sodium phosphate liposome lyophilized powder

目的利用壳聚糖作为载体将地塞米松磷酸钠(DSP)脂质体冻干粉剂导向结肠并探索载药脂质体经结肠黏膜吸收分布的规律性。方法用二次乳化法,经正交试验来筛选DSP脂质体的配方。测定脂质体的包裹率和载药量,观察脂质体的形态和粒径大小分布。建立HPLC测定DSP浓度的方法。制备DSP脂质体冻干剂,将其装入壳聚糖胶囊中,再以HPMCP包裹胶囊。分别给大鼠口服各种DSP制剂,测定经时血药浓度和结肠组织中分布量,计算药物的相对靶向释药指数(DDI)。结果用二次乳化法制备DSP脂质体时,平均包裹率为5482%,载药量为867%,粒径分布在120～265nm之间,平均粒径为178nm;口服给药时,和DSP粉剂壳聚糖胶囊或DSP溶液剂比较,DSP脂质体冻干剂壳聚糖胶囊被吸收入血的程度最低,而经时在结肠局部的分布程度最高。DSP壳聚糖胶囊结肠DDI分别是DSP溶液的2918和DSP壳聚糖胶囊的228。结论DSP脂质体冻干剂壳聚糖胶囊较DSP粉剂壳聚糖胶囊对结肠局部组织具有更好的定位释药作用和局部治疗效果,值得进一步开发研究。

OBJECTIVE: To investigate the absorption and distribution of chitosan capsule filled with dexamethasone sodium phosphate (DSP) liposome lyophilized powder in rats. METHODS: DSP liposome was prepared by duplicated emulsification method. Its formula was determined with the orthogonal experiment. The quality of DSP liposome, such as the encapsulation rate, drug-loading, morphology and size distribution, was estimated. The chosen liposome, made into its lyophilized powder, was then filled into the capsule coated with HPMCP. The capsules as well as the other DSP dosage forms were administered orally. Blood and colon tissue were collected periodically. The concentration of DSP was measured by HPLC, and used to calculate the relative targeting drug delivery index (DDI) of DSP. RESULTS: The prepared DSP liposome was characterized by its average encapsulation rate of 54.82% , drug-loading of 8.67% , and the size distribution from 120 nm to 265 nm (averaged 178 nm). After oral administration, the blood level of DSP lyophilized liposome capsule was the lowest in all the DSP dosage forms, but the distribution of DSP in colon was the highest. The relative targeting DDI of DSP lyophilized liposome capsule was 29.18 or 2.28, against DSP solution or DSP powder capsule, respectively. CONCLUSION: DSP lyophilized liposome chitosan capsule may be more helpful in treating colitis than DSP powder chitosan capsule. Hence, it is worth studying further.