The Application Of Electrospun Fibers Loaded With Chemotherapeutic Drugs In The Treatment Of Colon Cancer

In recent years,electrospinning technology has been widely used in the field of biomedicine,such as the drug-loaded carrier,tissue engineering scaffold and wound dressing.The electrospun fiber loaded with chemotherapeutic drug is a new type of drug release system.Electrostatic force traction is used to prepare the fiberous filaments.At the same time,the solvent is evaporated very fast and the chemotherapeutic drug is evenly loaded into the filaments.Due to the degradation of the polymeric matrix,the drug is slowly released from the fiberous membrane.Colon cancer ranks the third among the most common malignancies in the world.Currently,chemotherapy,radiotherapy and surgical resection are usually employed in cancer treatment.Among them,chemotherapy is the most commonly used for cancer treatment in clinical practice.However,the traditional chemotherapy often induces the nonspecific systemic distribution of chemotherapeutic drugs,resulting in limited therapeutic effects and serious side effects.This study fabricated a series of novel electrospun fibers loaded with chemotherapeutic drugs in the treatment of colon cancer.The research contents include the following three sections:(1)In the first section,we made knitted silk fibroin-reinforced bead-on-string electrospun fibers for sustained drug release towards the treatment of colon cancer.(Poly(lactic acid/glycolic acid),PLGA)was used as a carrier material for camptothecin(CPT)delivery,and fibers were fabricated on the surface of knitted silk fibroin(SF)using the electrospinning technology.The bead-on-string electrospun fibers with chemotherapeutic drugs were prepared in this experiment.Scanning electron microscope images showed that CPT was mainly distributed in beads of electrospun fibers.The drug release experiment indicated that the beaded electrospun fibers loaded with CPT exhibited sustained drug release profiles without burst drug release.In vitro experiments clearly suggested that meshes loaded with CPT could inhibit the growth of colon cancer cells efficiently.(2)In the second section,to improve the anti-colon cancer actively,we produced electrospun fibrous meshes by decoration with Pluronic F127(PF127).We prepared PLGA,PLGA-CPT and PLGA/PF127(with the mass ratios of 5:1,4:1 and 3:1)electrospun fibrous meshs by the electrospinning technology(abbreviated as PPC).Their physicalchemical properties had been characterized in details.We found that the introduction of PF127 to the meshes could increase sharply their drug loading and encapsulation efficiency.The drug loading of PPC membranes ranged from 5.6 to 6.8%.The corresponding encapsulation efficiencies were in the range from 83.0 to 88.9%.However,the drug loading and encapsulation efficiency of PLGA-CPT mesh were only 5.0% and 70.3%,respectively.In vitro drug release experiment showed that the introduction of PF127 to meshes significantly increased the drug release rate of the fibers in comparison with the control group.Furthermore,in comparison with PLGA-CPT mesh,the cell experiments further demonstrated that PPC fibers had a much stronger ability to inhibit the proliferation of CT-26 cells and the ability to induce apoptosis of cancer cells.(3)In the last section,we fabricated CPT/Curcumin(CUR)-co-loaded fibrous meshes for combination chemotherapy of colon cancer.Based on the electrospinning technology,we successfully prepared a series of PF127-modified CPT/CUR-loaded fiberous meshes.The morphological characterization showed that CPT and CUR were evenly distributed within the fibrous meshes.In vitro drug release experiments demonstrated that both types of drugs could be released from fibrous meshes simultaneously.The cell experiments showed that the combination index values of CPT/CUR(5:1,3:1 and 2:1)were all less than 0.5,indicating the synergistic effects of CPT and CUR.Furthermore,with the prolongation of cultivation time,the proliferation of CT-26 cells with chemotherapeutic drug-loaded fibrious mesh was significantly inhibited.Most importantly,CPT/CUR-loaded fibrous meshes exhibited much stronger anti-colon activities than the single drug-loaded formulations.Based on the above three experiments,we concluded that the electrospun fibrous membranes loaded with chemotherapeutic drugs could significantly improve the therapeutic effect of colon cancer.Furthermore,the further study demonstrated that CPT/CUR-co-loaded fibrous meshes for combination chemotherapy had much stronger anti-colon activities than the single drug-loaded fibrous meshes.