基于疏水性抗肿瘤药物载体构建超分子水凝胶

Micellar supramolecular hydrogel for delivery of hydrophobic anticancer drugs

目的:通过α-环糊精(α-CD)与聚乙二醇-聚己内酯两亲性嵌段聚合物(MPEG_(5 000)-PCL_(5 000))的自组装制备超分子水凝胶,并研究其作为疏水性抗肿瘤药物载体的可行性。方法:以紫杉醇(PTX)作为疏水性抗肿瘤药物研究对象,利用X-射线衍射(XRD)和扫描电子显微镜(SEM)表征载药水凝胶的结构,利用流变表征研究到链上环糊精的数量对其凝胶化时间、最终强度、溶涨率和降解速率的影响。结果:研究发现,PTX首先与MPEG_(5 000)-PCL_(5 000)形成稳定的复合物胶束,然后通过与α-CD的主客体作用将PTX原位包埋于凝胶中。体外释放实验表明,超分子水凝胶对药物分子的释放可以通过改变α-CD的数量进行调控。体外细胞实验证实,超分子水凝胶释放出的PTX有效抑制肿瘤细胞生长。结论:成功制备了负载抗肿瘤药物PTX的超分子水凝胶,其主要通过MPEG_(5 000)-PCL_(5 000)与α-CD的主客体相互作用。

Objective： To develop a micellar supra-molecular hydrogel composed of α-cyclodextrin（α-CD） and monomethoxy poly（ethylene glycol）-b-poly（e-caplactone）（MPEG5 000-PCL5 000） micelles and explore its feasibility for hydrophobic anticancer drug delivery. Methods： PTX as an object of hydrophobic antitumor drugs, drug-loaded supramolecular hydrogel was characterized by X-ray diffraction（XRD） and scanning electron microscopy（SEM）. The effect of α-CD amount on the gelation time, mechanical strength and thixotropic property was studied by a rheometer. Results： Pay-load of paclitaxel（PTX） to supramolecular hydrogel was achieved by encapsulation of PTX into MPEG5 000-PCL5 000 micelles prior mixing with α-CD aqueous solution. In vitro release study showed that the release behavior of PTX from hydrogel could be modulated by changing the α-CD amount in the hydrogel. Furthermore, such supramolecular hydrogel could sustain the releasing of encapsulated PTX compared to free PTX, as indicated by the cytotoxicity assay in vitro. Conclusion： Successful preparation of supramolecular hydrogels loaded with antitumor drug PTX, which mainly through interactions with α-CD.