Synthesis, Optimization and Characterization of Folate-Chitosan Polymer Conjugate for Possible Oral Delivery of Macromolecular Drugs

Abstract

Folate-chitosan (FA-CS) conjugate was assorted as a pharmaceutical approach to increase the cellular uptake of macromolecular drugs. It was synthesized by coupling the carboxylic group of the folic acid (FA) with the amino group of chitosan (CS) using carbodiimide. The designed conjugate was suggested to combine the mutual features of both FA and CS. Factors affecting the conjugation process was optimized using Box-Behnken design to maximize the amount of FA that could be coupled with CS. The influence of FA: CS ratio, reaction temperature and time on coupling ratio were studied. The prepared FA-CS conjugate was subjected to in-depth study including FT-IR, 1H NMR, mass spectroscopy, DSC, and XRD studies. The obtained conjugate was amorphous structure where the amount of conjugated folic acid was directly related to FA: CS ratio and the reaction time. On the contrary, increasing the reaction temperature negatively affect the coupling ratio of FA-CS polymer conjugate due to the possible thermal decomposition. The FA-CS conjugate is expected to enhance the intestinal uptake of macromolecular drugs and improve their oral bioavailability.