生物相容性温敏聚离子复合囊泡作为双重药物载体的研究

Polymer vesicles as a new drug carrier have many advantages including high loading capacity, good stability and capability of loading both hydrophilic and hydrophobic drugs. Mixing a pair of oppositely charged polyelectrolyte to form polyion complex vesicles introduce different segments into one system endowing them more functions. This project selects biocompatible CS, polyamino acid, hydrophilic PEG and stimuli-responsive monomers to synthesize double hydrophilic block and graft copolymers. Thermo- and pH-sensitive polyion complex vesicles with dual drug loading capacity are prepared by electrostatic interactions. Folic acid was used to conjugate on the surface of vesicles to realize the targeted transportation. Investigating the effect of chemical structures and environmental conditions on the drug release to summarize the relationship between responsive polyion complex vesicles with drugs and develop a simple and feasible method for new drug delivery system with high safety and efficiency. This study not only overcomes the current shortcomings of low and single drug loading, but also endows the targeted release and temperature/pH responsiveness to meet the requirement of controlled drug release. It provides the new ideas and basis for exploring a new drug delivery system suited for human body and promotes the applications in biomedical field.

聚合物囊泡作为一种新型药物载体具有内容量大、稳定性高、同时负载亲、疏水性药物的优点。由两种带相反电荷的亲水性共聚物，通过静电作用形成聚离子复合囊泡可将不同性质的链段引入到同一体系，赋予囊泡更多的功能。本项目选用生物相容性壳聚糖、聚氨基酸、亲水性聚乙二醇、温度敏感性单体制备全亲水嵌段和接枝共聚物，通过静电作用得到具有双重载药功能的聚离子复合囊泡，将叶酸修饰到囊泡表面，进一步提高载药囊泡的靶向性。研究聚合物组成、环境温度、pH值等条件对囊泡结构、载药量与释药速率的影响，总结聚离子囊泡与药物相互作用的规律，实现简便易行的方法构建安全、高效药物载体的途径。本研究不仅能克服当前药物载体载药量低，单一载药的不足，而且赋予靶向性和温度/pH敏感性，更好地满足药物控制释放的要求，为探索适合人体环境的新型药物输送体系，推动其在生物医学领域的应用提供新的思路和依据。

聚合物囊泡作为药物载体具有内容量大、稳定性高、同时负载亲/疏水性药物的优点。本项目选用生物相容性壳聚糖、海藻酸钠等天然高分子材料，利用温度敏感性聚合物对其接枝改性，通过静电作用制备了具有双重载药功能的聚离子复合囊泡，将亲/疏水性不同的药物负载到囊泡内部，研究了聚合物组成、环境温度、pH值等条件对囊泡结构、载药量与释药速率的影响。聚合物囊泡的粒径、结构稳定性、对药物的负载及释放性能可通过调节体系组成、环境温度、pH值或离子浓度等改变。该聚合物囊泡疏水性的膜和亲水性的空腔可同时负载5-氟尿嘧啶、阿霉素等亲/疏水性不同的药物。与聚合物胶束或其他传统药物载体相比，该体系中制备的聚合物囊泡对药物负载能力高（载药量40%以上，包封率90%以上），能够克服单一载药的不足，同时赋予载体温度/pH值双重敏感性，能够更好地满足高分子材料用于控制释放领域的要求，为探索应用于生物体内的新型药物输送体系提供了研究依据。