Programmable Codelivery of Doxorubicin and Apatinib Using an Implantable Hierarchical-Structured Fiber Device for Overcoming Cancer Multidrug Resistance.
Yang HeXilin LiJunkai MaGuoli NiGuang YangShaobing ZhouPublished in: Small (Weinheim an der Bergstrasse, Germany) (2019)
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.
Keyphrases
- multidrug resistant
- drug delivery
- cancer therapy
- transcription factor
- drug induced
- type diabetes
- papillary thyroid
- reactive oxygen species
- radiation therapy
- signaling pathway
- squamous cell carcinoma
- metabolic syndrome
- adverse drug
- circulating tumor cells
- computed tomography
- squamous cell
- pet imaging
- wound healing
- air pollution