Drug encapsulation and chiral recognition in deep eutectic solvents/β-cyclodextrin mixtures

Abstract

Hybrid materials resulting from the combination of Deep Eutectic Systems (DES) with well-known encapsulating agents like β-cyclodextrin (βCD) can open up new possibilities in the design of novel drug delivery systems or chiral-recognizing platforms. Here, 1:1 inclusion complexes of βCD and the tricyclic drugs amitriptyline (AMT) and cyclobenzaprine (CBZ) are studied in DES choline chloride:urea (reline) using a combination of NMR experiments. 1H complexation-induced chemical shift and intermolecular host-guest NOEs in the rotating frame (ROESY) confirm genuine drug encapsulation, and diffusion and relaxation measurements are used to study the dynamics of the guest-host inclusion complexes at the molecular level. Given the inherent chirality of AMT and CBZ, 13C NMR spectra unambiguously indicate the formation of diastereomeric inclusion complexes, demonstrating for the first time the retained enantiorecognition ability of βCD in DES. The proposed supramolecular systems combine then effectively the properties of DES and CDs.