紫杉醇聚合物纳米囊泡的制备和体外释放研究

目的 以聚己内酯-b-聚乙二醇-6-聚己内酯（PCEP）两亲性三嵌段共聚物为载体研制紫杉醇聚合物纳米囊泡.方法 以不同分子量的聚乙二醇（PEG）引发合成不同亲水段、疏水段链长的PCEP并进行FT-IR、1H NMR和GPC表征,以合成的嵌段聚合物PCEP为载体,通过薄膜-超声分散法制备紫杉醇聚合物纳米囊泡,用透射电子显微镜（TEM）表征其形态和构造,用粒度分析仪测定其粒径及分布,用高效液相色谱（HPLC）法测定其载药量及包封率,用透析袋法研究药物体外释放;同时,研究不同亲水链长、疏水链长对紫杉醇聚合物囊泡载药量、包封率、粒径及体外释放紫杉醇药物的影响.结果 研制的紫杉醇聚合物囊泡呈核-壳结构球形,粒径为纳米级,随着PCEP共聚物相对分子质量的增加而增大;紫杉醇聚合物囊泡体外释放无突释现象,能稳定缓慢释放紫杉醇,且释放速率随共聚物中亲水段PEG含量增加而增大,随疏水段PCL含量增大而减小.结论 以PCEP两亲性三嵌段共聚物为载体制备的紫杉醇聚合物纳米囊泡,其粒径小且分布均匀,包封率较高,有望成为一种用于提高紫杉醇的药效且降低不良反应的新的紫杉醇缓控释剂型.

Preparation, characterization and in vitro release of paclitaxol-loaded polymersomes

Objective To develop paclitaxol (PTX)-loaded polymersomes based on poly (ε-caprolactone)-block-poly (ethylene glycol)-block-poly (ε-caprolactone)(PCL-b-PEG-b-PCL, PCEP) amphiphilic triblock copolymers. Methods A series of PCEP copolymers was synthesized by ring-opening polymerization of ε-caprolactone initiated by PEG. The block copolymers were characterized by FT-IR、1H NMR and GPC. PTX-loaded polymersomes were prepared by thin-film and ultrasonic dispersion method and characterized in terms of morphology,particle size and size distribution, encapsulation efficiency and in vitro release. The effect of different hydrophilic and hydrophobic chain length on the drug-loading content, entrapment efficiency, size and size distribution and in vitro release were also investigated. Results The PTX-loaded polymersomes showed nanometer size and spherical morphology with core and shell. The sizes of PTX-loaded polymersomes increased with the increasing of the molecular weight of PCEP. The PTX-loaded polymersomes showed a continuous and steady release of PTX without initial burst release. The release rate increased with the increasing of hydrophilic PEG chain content and decreased with the increasing of hydrophobic PCL chain content. Conclusion For the first time, a novel PTX-loaded polymersomes was developed based on PCL-b-PEG-b-PCL amphiphilic triblock copolymers. The PTX-loaded polymersomes showed nanometer size, narrow size distribution and high drug encapsulation efficiency.These results indicate that PTX-loaded polymersomes could be a promising novel controlled release dosage form to increase therapeutic effect with decreased toxic and side effect of PTX.