β-Cyclodextrin Nanosponge Hydrogels as Drug Delivery Nanoarchitectonics for Multistep Drug Release Kinetics

The reaction of beta-cyclodextrin with suitable bifunctional cross-linkers (such as carboxylic acids dianhydrides) provides 3D nanoporous polymers referred to as cyclodextrin nanosponges (CDNS). The swelling ability of many CDNS can be exploited to confine small active molecules, such as drugs, in the resulting hydrogel, thus providing drug-loaded CDNS hydrogels. This raises an increasing interest toward CDNS hydrogels as biomaterials for controlled drug delivery due to their nontoxicity, biocompatibility, and biodegradability. The release kinetics of a drug carrier is often influenced by the physical and chemical properties of the hydrogel nanoarchitectonics and the drug-polymer interactions across the 3D network. A deep understanding, at the molecular level, of the mechanisms underlying drug dynamics in the hydrogel polymer matrix and the relation with the macroscopic release kinetic is a key step for a rational design of delivery systems. In this study, nanosponge-hydrogels are prepared by cross-linking beta-cyclodextrin with pyromellitic dianhydride and swelling the corresponding polymer loaded with the anti-inflammatory drug piroxicam. The translational dynamics of the small drug in the optimized hydrogel formulation are investigated by H-1 high resolution magic angle spinning (HR-MAS) NMR spectroscopy at variable observation times. The microscale results, compared with in vitro release kinetics performed on a much longer time-range, reveal a continuous Fickian dynamics of the drug within the 3D polymer network. The multistep prolonged release of the drug is influenced in a combined mode by the polymer nanoarchitectonics with adsorption of the drug-to-polymer network and beta-cyclodextrin-drug complex formation.

Automated summary

Cyclodextrin nanosponges (CDNS) are 3D nanoporous polymers formed by reacting beta-cyclodextrin with suitable bifunctional cross-linkers, which can be used as biomaterials for controlled drug delivery due to their nontoxicity, biocompatibility, and biodegradability. The release kinetics of a drug carrier in CDNS hydrogels are influenced by the nanoarchitectonics of the hydrogel and the interactions between drug and polymer across the 3D network.