本发明公开了一种电荷驱动自组装壳聚糖基载药纳米粒子的制备方法,包括以下步骤：(1)通过氨基PEG诱导的谷氨酸苄酯-N-羰基环内酸酐,形成PEG和聚谷氨酸苄酯的嵌段共聚物,该嵌段共聚物在碱性条件下水解,去除聚谷氨酸苄酯端的苄基,形成PEG-PGA嵌段共聚物；(2)壳聚糖基阿霉素前药制备；(4)电荷驱动自组装纳米粒子制备。本发明制备载阿霉素壳聚糖基纳米粒子的策略选用的材料是已经被普遍证明具有较好的生物相容性PEG和PGA材料,形成壳聚糖纳米粒子的策略具有较好的生物相容性和生物医用前景。

Chitosan (CS) based nanoparticles (NPs) have several advantages in delivering drugs. They are usually prepared in a microemulsion solvent system but this route can leave significant levels of potentially harmful organic solvent residue in the NPs. In this study, we prepared CS based nanocomposites using charge driven self-assembly in an aqueous buffer, thus avoiding the use of organic solvents. Doxorubicin (DOX) was covalently attached to positive charged CS with a legumain substrate peptide to confer targeted drug release property, since legumain is often overexpressed in tumors or tumor associated micro environments. This DOX prodrug solution interacted with negative charged methoxyl poly (ethylene glycol)-block-poly (glutamic acid) copolymer (PEG-PGA) in an aqueous buffer forming nanocomposite with a regular morphology.