H-ESO-HEC两亲性聚合物的合成及其自组装纳米胶束在疏水性药物载体中的应用

Synthesis of H-ESO-HEC amphiphilic copolymers and their self-assembled nanomicelles as aqueous carriers for hydrophobic drugs

在二甲基亚砜(DMSO)溶液中,以羟乙基纤维素(HEC)为亲水链段,环氧大豆油(ESO)为疏水链段,在催化剂四氯化锡的作用下合成羟乙基纤维素接枝环氧大豆油(ESO-HEC),ESO-HEC经氢氧化钠水解后得到一系列羟乙基纤维素接枝环氧大豆油水解聚合物(H-ESO-HEC)。研究了亲水链段分子质量和疏水链段用量对聚合物自组装行为和包载能力的影响。利用FT-IR、1 H-NMR、TGA、TEM、DLS和荧光光谱等技术对H-ESO-HEC两亲性聚合物的结构、物理性能以及自组装行为进行表征。结果表明,H-ESO-HEC两亲性聚合物在水溶液中可自组装形成均一的球形纳米胶束,平均粒径范围为97~221nm,临界胶束质量浓度为292~336μg/mL。以疏水性抗癌药物紫杉醇和吴茱萸碱作为模型药物,利用超声-透析法实现了胶束对药物的包载,纳米胶束对紫杉醇和吴茱萸的包封率随疏水链段用量或亲水链段分子质量的增加而增加,最大包封率可达69.1%和62.9%。

Epoxidized soybean oil grafted hydroxyethyl cellulose(ESO-HEC)was synthesized via grafting reaction between hydrophobic epoxidized soybean oil(ESO)and hydrophilic hydroxyethyl cellulose(HEC)with stannic chloride as catalyst in dimethyl sulfoxide(DMSO).A series of hydrolyzed H-ESO-HEC copolymers were prepared after hydrolyzing the ESO-HEC with sodium hydroxide.The effects of molecular weights of hydrophilic segments and the amounts of hydrophobic segments in H-ESO-HEC copolymers on their self-assembly behaviors were evaluated.The chemical structures,physical properties and self-assembly behaviors of copolymers were characterized by FT-IR,1H-NMR,TGA,TEM,DLS and fluorescence spectroscopy.The results indicated that H-ESO-HEC copolymers were able to self-assemble into spherical nano-micelles with an average particle sizes ranging from 97 to 221 nm and a critical micelle concentration of 292 to 336μg/mL.The hydrophobic paclitaxel and evodiamine were used as model drugs in order to investigate drug loading ability of H-ESO-HEC micelles.With the increasing of the hydrophobic lengths,the encapsulation efficiencies of paclitaxel and evodiamine in micelles were increased.The highest encapsulation efficiencies of paclitaxel and evodiamine in nanomicelles were 69.1%and 62.9%,respectively.