2-Methyl-β-cyclodextrin grafted ammonium chitosan: synergistic effects of cyclodextrin host and polymer backbone in the interaction with amphiphilic prednisolone phosphate salt as revealed by NMR spectroscopy

Abstract Reduced molecular weight chitosan was quaternized with 2-chloro-N,N-diethylethylamine to obtain a water soluble derivative (N+-rCh). Methylated-β-cyclodextrin (MCD), with 0.5 molar substitution, was covalently linked to N+-rCh through 1,6-hexamethylene diisocyanate spacer to give the derivatized ammonium chitosan N+-rCh-MCD. To shed light on the role of the cyclodextrin pendant in guiding binding interactions with amphiphilic active ingredients, corticosteroid prednisolone phosphate salt (PN) was considered. The deep inclusion of PN into cyclodextrin in PN/MCD model system was pointed out by analysis of 1H NMR complexation shifts, 1D ROESY spectra, and diffusion measurements (DOSY). By using proton selective relaxation rates measurements as investigation tool, the superior affinity of N+-rCh-MCD towards PN was demonstrated in comparison with parent ammonium chitosan N+-rCh.