| Cancer is a leading cause of human deaths. Chemotherapy has been a major treatment methodology for malignant tumors. 5-FU, as one of the oldest and best antineoplastic chemotherapy drugs, has been used in clinical practices for decades. 5-Fu is an active medicine against many cancers such as Colon, Breast, Stomach and Pancreas cancers. However, current practice of this chemotherapy comes with severe side effects including diarrhea, low white blood counts, low platelet counts and anemia etc. Therefore, the life quality of the patients being treated with often deteriorates within in a rather short period. The main reason is that both the target cancerous cells and normal cells are subject to none-selective expose to the drug which leads to unwanted toxic side effects.In order to improve the cancer-targeting and selective activity of antineoplastic agent, 5-fluorocracil (5-FU), a novel pH-responsive drug delivery system (DDS), pullulan acetate/sulfonamide (PA/SDM) conjugate, was synthesized by a diafiltration method. Sulfonamide was grafted to the hydrophobically modified pullulan acetate (PA) to enhance the pH sensitivity for better cancer-targeting delivery. 5-Fu was loaded into the self-assembled nanoparticles by the same method. The drug-loaded self-assembled nanoparticles were successfully obtained and characterized in terms of particle size, morphology and drug loading and release profile at various pHs. The results showed that the mean diameters of the self-assembled particles were approximately 100nm, with uniform size distribution and good sphere morphology. The nanoparticles showed good stability at pH 7.4 which is equal to the normal body fluid pH, but shrank and aggregated below pH 6.8 which is close to the pH of the tumors. The loading efficiency and concentration of released 5-FU was monitored at 269 nm on the UV/Vis spectrophotometer. The release profile was heavily pH-dependent around physiological pH, and the release rate was significantly enhanced under pH of 6.8.
|
PDF Full Text Request