Targeted and sustained delivery of drugs to diseased tissues/organs, where body fluid exchange and catabolic activity are substantial, is challenging due to the fast cleansing and degradation of the drugs by these harsh environmental factors. Herein, a multifunctional and bioadhesive polycaprolactone‐β‐cyclodextrin (PCL‐CD) polymersome is developed for localized and sustained co‐delivery of hydrophilic and hydrophobic drug molecules. This PCL‐CD polymersome affords multivalent crosslinking action via surface CD‐mediated host–guest interactions to generate a supramolecular hydrogel that exhibits evident shear thinning and efficient self‐healing behavior. The co‐delivery of small molecule and proteinaceous agents by the encapsulated PCL‐CD polymersomes enhances the differentiation of stem cells seeded in the hydrogel. Furthermore, the PCL‐CD polymersomes are capable of in situ grafting to biological tissues via host–guest complexation between surface CD and native guest groups in the tissue matrix both in vitro and in vivo, thereby effectively extending the retention of loaded cargo in the grafted tissue. It is further demonstrated that the co‐delivery of small molecule and proteinaceous drugs via PCL‐CD polymersomes averts cartilage degeneration in animal osteoarthritic (OA) knee joints, which are known for their biochemically harsh and fluidically dynamic environment.

中文翻译：

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通过超分子宿主-客体复合物在具有苛刻酶和流体环境的病理部位进行局部和持续药物递送的生物粘附性聚合物囊泡

由于这些恶劣的环境因素导致药物的快速清洗和降解，将药物有针对性地和持续地输送到患病组织/器官中时，体液交换和分解代谢活动非常重要。本文中，开发了一种多功能且具有生物粘附性的聚己内酯-β-环糊精（PCL-CD）聚合物囊泡，用于亲水性和疏水性药物分子的局部和持续共递送。这种PCL‐CD聚合物囊泡通过表面CD介导的主客体相互作用提供多价交联作用，生成超分子水凝胶，表现出明显的剪切稀化和有效的自我修复行为。包封的PCL-CD聚合物囊泡与小分子和蛋白物质的共同输送增强了植入水凝胶中的干细胞的分化。此外，PCL-CD聚合物囊泡能够通过体外和体内表面CD和组织基质中天然客体之间的宿主-客体复合原位移植到生物组织，从而有效地延长了负载的货物在移植组织中的保留时间。进一步证明，通过PCL-CD聚合物小体与小分子和蛋白质类药物的共同给药可避免动物骨关节炎（OA）膝关节中的软骨变性，而软骨变性以其生化恶劣和流体动力学环境而著称。