Investigation On Polymeric Short Fibers And The Controlled Release Of Anticancer Drugs

Cancer is one of the major diseases affecting human lives. Surgical removal combined with radiotherapy and chemotherapy is mainly used to treat cancer, but adjuvant therapy of chemotherapeutical drugs by intravenous injection has many shortcomings, such as fast drug metabolism, low bioavailability and severe side effects. In order to overcome these shortcomings, target delivery and controlled release of chemotherapeutic drugs have observed extensive research on spherical carrier, such as liposomes, micelles, polymersomes and nanoparticles. Spherical carriers can reduce the side effect of chemotherapeutic drugs and improve the bioavailability to some extent. But after intravenous injection spherical cargoes are easy to be cleared from circulating and difficult to reach tumor tissues and enter tumor cells. In nature, a number of viruses that infect animals are likewise filamentous, providing additional motivation for the development and study of filamentous vehicles. In the current work, micrometer-sized fibrous rods were designed as drug carriers, and broad-spectrum anticancer drug doxorubicin (DOX) was losed to investigate the cellular uptake, tissue distribution and antitumor effects.C6-loaded PSMA fibrous rods with different aspect ratio were prepared by electrospinning combined with ultrasonication treatment. The diameter of fibers is about 500 nm, and the aspect ratio of fibers can be controlled between 5-20. C6/PSMA microspheres were also prepared by the solvent evaporation process, and the average diameter was close to that of fibrous rods. The result of cellular uptake illustrated that fibrous rods were easier uptaken by breast cancer cells 4T1, and the uptake efficiency was lower for RAW264.7 macrophages. In vivo distribution displayed that microspheres were mostly accumulated in liver and spleen, while fibrous rods were mainly accumulated in lung. This result demonstrated fibrous rods can escape from the reticuloendothelial (RES) system to soame extent. DOX-loaded PELA fibrous rods and microspheres were prepared though the same process. In vitro release tests showed that DOX was released continuously from both from fibrous rods and microspheres. DOX/PELA fibrous rods with different aspect ratios showed similar release behaviors. Cellular uptake of DOX/PELA fibers and microspheres assay showed the highest internalization amount was detected for fibrous rods with an aspect raio of around 2. Cytotoxicity assay displayed both fibrous rods and microsphere can enhance the toxicity to 4T1.Pharmacokinetics analysis showed that fibrous rods persisted in the circulation up to one week, and improved the bioavailability of the drugs greatly. Treatment on breast tumor models indicated that DOX-loaded fibrous rods not only decreased the systemic toxicity but also enhance the antitmuor and antimetastasis efficacies.