Activation of a gamma-cyclodextrin-based metal-organic framework using supercritical carbon dioxide for high-efficient delivery of honokiol

A facile method for the activation of gamma-cyclodextrin metal-organic framework (CD-MOF) without channel blockage and framework collapse was first developed using supercritical carbon dioxide (scCO(2)), which enabled higher surface area and larger pore volume. The scCO(2)-assisted impregnation method was also applied to introduce the insoluble drug, honokiol (HNK), into the pores of CD-MOF with higher cargo loading compared to the conventional liquid phase incorporation in ethanol. Notably, the resulting HNK-loaded CD-MOF (HNK@CD-MOF) had improved apparent solubility and enhanced dissolution rate. The intestinal cellular uptake and transport experiments demonstrated that CD-MOF could enhance cellular uptake and increase drug transport across the intestinal epithelial cells compared to the cyclodextrin inclusion complex. Moreover, the in vivo pharmacokinetic studies further confirmed that CD-MOF could significantly improve the oral absorption and bioavailability of HNK. Overall, the scCO(2) activation and scCO(2)-assisted impregnation approaches were demonstrated as promising strategies to maximize the potential capability of CD-MOF.