Programmable Codelivery of Doxorubicin and Apatinib Using an Implantable Hierarchical‐Structured Fiber Device for Overcoming Cancer Multidrug Resistance

다국어 초록 (Multilingual Abstract)

Multiple drug resistance (MDR) of cancer cells is a major cause of chemotherapy failure. It is currently a great challenge to develop a direct and effective strategy for continuously inhibiting the P‐glycoprotein (P‐gp) drug pump of MDR tumor cells, thus enhancing the intracellular concentration of the therapeutic agent for effectively killing MDR tumor cells. Here, a new implantable hierarchical‐structured ultrafine fiber device is developed via a microfluidic‐electrospinning technology for localized codelivery of doxorubicin (DOX) and apatinib (AP). An extremely high encapsulation efficiency of ≈99% for the dual drugs is achieved through this strategy. The release of the loaded dual drugs can be controlled in a programmable release model with a rapid release of the micelles, while AP is slowly released. The sustained release of AP can continuously inhibit the P‐gp drug pump of MDR tumor cells, increasing the intracellular DOX accumulation. The in vivo DOX biodistribution displays that the DOX accumulation in the tumor tissues achieves 17.82% after implanting the fiber device for 72 h, which is 6.36‐fold higher than that of the intravenously injected DOX. Importantly, the fiber device shows an excellent antitumor effect on MDR tumor‐bearing mice with low systemic toxicity.
An implantable hierarchical‐structured ultrafine fiber device is successfully developed, which codelivers dual drugs in a programmable release pattern. The device achieves extremely high drug accumulation in tumor tissue and is capable of continuously inhibiting the P‐glycoprotein drug pump of multiple drug resistance (MDR) tumor cells, thus effectively reversing the MDR for enhancing chemotherapy efficiency.