Cyclodextrin Metal–Organic Frameworks as a Drug Delivery System for Selected Active Pharmaceutical Ingredients
Kristīne Krūkle‐Bērziņa, Alons Lends, Anna Boguszewska‐Czubara
Abstract
High Resolution Image Download MS PowerPoint Slide The cyclodextrin-based metal–organic frameworks (CD MOFs) are a suitable molecular platform for drug delivery systems of various active pharmaceutical ingredients (APIs). The low toxicity and cost-efficient synthesis make CD MOFs an attractive host for the encapsulation of APIs. In this study, we created a model system based on γCD-K MOFs with widely used drugs carmofur (HCFU), 5-fluorouracil (5-FU), and salicylic acid (HBA) to study host–guest encapsulation methods using different crystallization protocols. The host–guest complexes of API:CD MOF in an in-depth study were investigated by liquid chromatography–mass spectrometry (LC-MS), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and 19 F- and 13 C-detected solid-state NMR spectroscopy (ssNMR). These techniques confirmed the structure and interaction sites within the encapsulation product in the host–guest complex. We also evaluated the toxicity and biocompatibility of the API:CD MOF complex using in vitro and in vivo methods. The cytotoxicity, hepatotoxicity, and neurotoxicity were established with cell lines of fibroblasts (BJ), human liver cell line (HepG2), and human oligodendrocytic cells (MO3.13). Then, Danio rerio was used as an in vivo experimental model of ecotoxicity. The results showed the choice of γCD-K-5 as the most protective and safe option for drug encapsulation to decrease its toxicity level against normal cells.