Polycomponent metal-organic frameworks of substituent polydispersion hydroxypropyl-β-cyclodextrin as inhalable drug carrier

Abstract

Cyclodextrin metal-organic frameworks (CD-MOFs) have garnered considerable attention for their unique porous structure, outstanding properties and diverse pharmaceutical applications. To date, all reported CD-MOFs have been synthesized using natural cyclodextrins (CDs) with periodic structures as organic ligands, while the most widely applied CD derivatives like hydroxypropyl-β-cyclodextrin (HCD) have not been used as organic ligands for MOFs formation. Herein, we showed that the substituent polydispersion HCD coordinated with sodium ions to form polycomponent metal-organic frameworks (HCD-pMOFs), in which up to 21 stochastically substituted hydroxypropyl groups on each HCD resulted in compositional disorder. Multiple coordination modes between HCD and sodium ions resulted in the formation of cavities with sizes of 2.65 nm and 3.40 nm. It was hypothesized that the supramolecular structural units of HCD-pMOFs were constructed based on the molar ratio of HCD and sodium ions. Additionally, HCD-pMOFs exhibited the ability to improve thermal stability via solidification of volatile components, as conclusively demonstrated through eugenol stabilization experiments. In inhalation drug delivery applications, HCD-pMOFs showed excellent in vitro deposition performance and inhalation safety. Consequently, the synthesis of HCD-pMOFs furnishes a strategy for the MOFs made of derivatized cyclodextrins, and presents a novel type of carriers for inhalation drug delivery.

Keywords: Hydroxypropyl-β-cyclodextrin; Inhalation delivery; Metal-organic frameworks; Polycomponent; Polydispersion.