Development and characterization of mucoadhesive nanoparticles based on hyaluronic acid for colon specific release of methotrexate

Abstract

Colorectal cancer is the third highest worldwide incidence between men and women. Despite advances in antineoplastic therapy, cancer remains a stigma for society causing severe damage to the patients quality of life. The intravenous chemotherapy is widely used and is the first choice treatment for the most cases. When administered, only a small fraction of the chemotherapeutic agent reaches the tumor tissue, the rest is distributed among the healthy organs and tissues, reducing the treatment effectiveness and causing severe side effects. Methotrexate (MTX) is a classic folic acid antagonist and one of the most commonly used therapeutic agent for the solid tumors treatment. The targeting of MTX for colon region, where the tumor is located, as well as the specific and prolonged interaction of the drug with the action site is a rational and promising strategy to improve the treatment efficacy and to reduce the side effects. In this context, nanoparticles of chitosan, hyaluronic acid and hydroxypropylmethylcellulose phthalate, containing MTX will be developed by polyelectrolytic complexation and characterized through the analysis of entrapment efficiency, size, shape, zeta potential, infra red absorption spectroscopy, thermal properties (DSC and TG) and mucoadhesive properties. The performance of the nanoparticles as a controlled release system of MTX will be evaluated by the in vitro release profile, in media with pH values that mimic the different portions of the GIT, followed by determination of the drug release mechanisms.