Multifunctionalized systems-based chitosan nanoparticles anchored with methotrexate and incorporated into resistant starch/pectin microparticles for colon-specific release of 5-fluourouracil

Abstract

The treatment of the colorectal cancer is conducted by administering high doses of antineoplasic agents due to its lack of specificity, leading to severe side effects. Among these drugs, 5-fluorouracil is one of the more effective and although suffers first pass metabolism its efficacy may be enhanced by combination with methotrexate, which due to structural similarity with folic acid, promotes internalization by the cancerous cells. The improvement of the residence time of the drug in the tumor tissue can be achieved using nanoparticles, which due its small size favor the system penetration through the tumor vessels and mucus layer. The use of chitosan for the development of nanoparticles should be highlighted due their important mucoadhesive properties. The nanoparticles can be incorporated into microparticles based on natural polysaccharides with biodegradability dependent on colonic enzymes, as resistant starch and pectin, in order to reach its colon specific release and to promote the local action of 5- fluorouracil, minimizing side effects. In this sense, the development of chitosan nanoparticles functionalized with methotrexate and incorporated in resistant starch/pectin microparticles for oral administration is a potential strategy for colonic release of 5-fluorouracil, leading to increased anti-tumor activity and optimization of the treatment of colorectal cancer. (AU)