Effects of folic acid esterification on the hierarchical structure of amylopectin corn starch

There are burgeoning research interests in designing biocompatible colloidal delivery systems for treating as well as delaying the recurrence of chronic diseases, including various forms of cancers. In this respect, folic acid (FA) esters and starch are particularly interesting owing to (i) the molecular recognition of FA by folate receptors and (ii) the biocompatibility of starch based delivery systems. In this study, the effects of esterification of amylopectin corn starch (ACS) with FA using an n, n’-dicyclohexylcarbodiimide/4-dimethylaminopyridine (DCC/DMAP) mediated esterification reaction were investigated at multiple length scales. Scattering (light, X-ray), spectroscopy (FTIR), electrophoretic mobility (ζ-potential) and confocal laser scanning microscopy (CLSM) confirmed that structural rearrangements (short- and long-range) occurred in the starch-folic acid ester (SF) derivatives with increased FA content (degree of substitution, 0.01–0.05). The SF ranged in size from 200 to 600 nm and were negatively charged (ca. −24 mV, SF20). FTIR revealed a loss of double-helical structure on FA substitution. Notably, CLSM and small angle X-ray scattering (SAXS) both showing an FA-assisted self-assembly and crosslinking of SF, later confirming columnar assemblies with unit cell parameter of 4.5 nm. The wide-angle X-ray scattering (WAXS) and X-ray diffraction (XRD) pattern (2θ = 6.1°, 7.7°, 13°, 17°, 20°, 22°, and 25°) in SF further gave evidence for the formation of hybrid B and V-type polymorphs, where SF may accommodate FA within a larger hybrid hexagonal lattice. This study provides structural insights for developing tunable starch-folic acid derivatives for potential applications as delivery vehicles for pharmaceuticals and nutraceuticals targeting folate receptors.