mPEG-PCL聚合物囊泡的制备及INS-mPEG114-PCL152囊泡体外释放特性考察

Preparation of mPEG-PCL Polymersomes and in Vitro Release Investigation of Insulin-loaded mPEG114-PCL152 Polymersomes

摘要:

目的: 合成聚乙二醇单甲醚-聚己内酯(mPEG-PCL)嵌段聚合物,制备聚合物囊泡并考察胰岛素(INS)-mPEG₁₁₄-PCL₁₅₂的体外释药行为. 方法: 利用开环反应制备不同相对分子质量的mPEG-PCL聚合物并对其结构进行表征确定.采用薄膜水化法制备聚合物囊泡,激光散射法测定粒径,透射电镜考察表观形态,芘荧光探针法测定临界聚集浓度值(CAC).利用Bradford法测定INS-mPEG₁₁₄-PCL₁₅₂的载药情况及其体外释放行为. 结果: 空白囊泡粒径约200 nm,CAC均较小.20%投药比例制备的载药囊泡模型药物INS-mPEG₁₁₄-PCL₁₅₂利用度最大,包封率(62.80±2.14)%,载药量(11.10±0.34)%;体外释药考察前2 h突释19.28%,48 h后累积释药55.05%,符合Higuchi模型. 结论: mPEG-PCL共聚物囊泡粒径适中,抗稀释能力强.INS-mPEG₁₁₄-PCL₁₅₂具有较明显突释效应,随着表面结合的INS的解离,逐渐呈良好缓释作用.

Abstract:

Objective: To prepare mPEG-PCL copolymer and polymersomes,then investigate in vitro release of INS-mPEG₁₁₄-PCL₁₅₂ polymersomes. Method: mPEG-PCL block copolymer was synthesized by ring-opening polymerization method,chemical structure of these polymers were characterized by FT-IR and ¹H-NMR.Polymersomes were prepared by film hydration method,particle size and apparent morphology were examined by dynamic light scattering and transmission electron microscope,respectively;critical aggregation concentration(CAC) was detected by fluorescence techniques with pyrene as a probe.Encapsulation efficiency,drug loading and in vitro release characteristic of INS-mPEG₁₁₄-PCL₁₅₂ polymersomes were determined by Bradford method. Result: Average particle sizes of blank polymersomes were about 200 nm,CAC were all low value.These prepared INS-mPEG₁₁₄-PCL₁₅₂ with 20% drug-copolymer ratio had maximize utilizaiton ratio,average encapsulation efficiency (62.80±2.14)% as well as drug loading (11.10±0.34)%.In vitro cumulative release of INS-mPEG₁₁₄-PCL₁₅₂ polymersomes in 48 h was about 55.05%,with relatively significant burst release at initial 2 h about 19.28%. Conclusion: These polymersomes have uniform particle size with a great anti-dilution capability.INS-mPEG₁₁₄-PCL₁₅₂ polymersomes show a significant burst release at initial stage and then a good sustained-release property with dissociation of surface model drug.