Department of Chemistry and Industrial Chemistry, University of Pisa, via Moruzzi 13, 56124 Pisa, Italy.
Department of Pharmacy, University of Pisa, via Bonanno 33, 56126 Pisa, Italy.
Int J Pharm. 2020 Sep 25;587:119698. doi: 10.1016/j.ijpharm.2020.119698. Epub 2020 Jul 28.
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 H 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.
低分子量壳聚糖与 2-氯-N,N-二乙基乙胺季铵化，得到水溶性衍生物（N-rCh）。用 1,6-己二异氰酸酯间隔臂将 0.5 摩尔取代的甲基-β-环糊精（MCD）共价连接到 N-rCh 上，得到衍生化的铵壳聚糖 N-rCh-MCD。为了阐明环糊精侧链在引导与两亲性活性成分结合相互作用中的作用，选择了皮质甾类药物磷酸泼尼松盐（PN）。通过分析 H NMR 络合位移、1D ROESY 光谱和扩散测量（DOSY），指出了 PN 在 PN/MCD 模型系统中环糊精中的深度包合。通过使用质子选择性弛豫率测量作为研究工具，与母体铵壳聚糖 N-rCh 相比，证明了 N-rCh-MCD 对 PN 的超亲和力。
