【摘要】 以普朗尼克F127-聚丙烯酸聚合物(PF127-PAA)和普朗尼克P123(PP123)为载体制备紫杉醇(PTX)口服聚合物胶束,考察其理化性质、体外释药行为,并对其在大鼠肠道的吸收进行探究。首先合成了PF127-PAA,并通过FT-IR、1H-NMR对其结构进行确证;用薄膜水化法制备紫杉醇口服聚合物胶束,并在单因素考察的基础上,以均匀设计-效应面优化法进行处方优化;通过透射电镜观察胶束的形态,并用粒径和Zeta电位分析仪测定胶束的粒径及Zeta电位,高效液相色谱法测定胶束的载药量和包封率;采用动态膜透析法研究胶束的体外释药行为;以大鼠在体肠灌流技术考察胶束在大鼠肠道的吸收情况。结果:制备的紫杉醇口服聚合物胶束的外形大致呈球形,平均粒径为23.7 nm,Zeta电位为1.54 m V,载药量为1.88%,包封率为76.50%。体外释放结果表明,普朗尼克F127-聚丙烯酸/普朗尼克P123(PF127-PAA/PP123)紫杉醇胶束的释放优于普朗尼克F127/普朗尼克P123(PF127/PP123)紫杉醇胶束,将PAA引入胶束后,有促进紫杉醇释放的作用。肠吸收实验中,与紫杉醇原料药相比,PF127-PAA/PP123紫杉醇胶束的吸收速率常数Ka和吸收百分率P均得到明显提高。PF127-PAA/PP123聚合物胶束能有效增溶紫杉醇,增加紫杉醇的肠道吸收,在紫杉醇口服给药系统中有良好的应用前景。更多还原

【Abstract】 Paclitaxel( PTX) loaded oral polymer micelles were prepared with Pluronic F127-poly( acrylic acid) copolymer( PF127-PAA) and Pluronic P123( PP123). The physico-chemical properties,in vitro release behaviors and in situ intestinal absorption in rats of the micelles were investigated. The PF127-PAA copolymer was synthesized and the chemical structure was confirmed by FT-IR and1H-NMR. PTX-loaded oral micelles were prepared by the thin film hydration method. Based on the results of single-factor experiments,the best formulation of PTX-loaded oral micelles was optimized by the uniform design-response surface methodology. The PTXloaded oral micelles were characterised by transmission electron microscopy for morphological properties,dynamic light scattering and electrophoretic scattering for size and size distribution and zeta potential and high performance liquid chromatography( HPLC) for the drug-loading coefficient( DL%) and entrapment efficiency( EE%) of PTX in micelles. The in vitro release behaviors of PTX-loaded oral micelles were carried out by the dynamic membrane dialysis technique and the absorption of PTX-loaded oral micelles in the intestinal tract was studied via an in situ perfusion method in rats. Most of the PTX-loaded oral micelles were presented as spherically shaped under transmission electron microscopy,with an average diameter of 23. 7 nm. The zeta potential of PTX-loaded oral micelles was 1. 54 m V,while the DL% as well as the EE% were 1. 88% and 76. 50%,respectively. In vitro drug release studies found that PTX-loaded Pluronic F127-poly( acrylic acid) / Pluronic P123( PF127-PAA / PP123) micelles were superior to that of PTX-loaded Pluronic F127 / Pluronic P123( PF127 / PP123) micelles,which suggested that PAA could facilitate the release of PTX from micelles.The results of in situ intestinal absorption showed that,compared with the PTX solution,the values of absorption rate constant( Ka)and the drug percentage absorbed( P) of PTX-loaded PF127-PAA / PP123 micelles were significantly higher. The PF127-PAA / PP123 oral micelles can obviously improve the solubility of PTX and increase the absorption of PTX in the intestinal tract,and may serve as a potiential oral drug delivery system for a poorly water-soluble drug PTX.更多还原