Vapor-Phase-Mediated Encapsulation of Guest Drug Molecules in the Hexagonal Columnar Form Structure of Polyethylene Glycol/-Cyclodextrin-Polypseudorotaxane

The drug/(PEG/& gamma;-CD-PPRX) complex is a unique multicomponentsupramolecular structure where the drug molecules are incorporatedin the intermolecular spaces of the polypseudorotaxane (PPRX) preparedfrom polyethylene glycol (PEG) and & gamma;-cyclodextrin (& gamma;-CD).Herein, we report a sealed-heating preparation method to obtain anunanticipated polymorphic form of the drug/(PEG/& gamma;-CD-PPRX) complex,which is the hexagonal-columnar (HC) form. The encapsulation efficiencyof the six guest drugs was evaluated. The crystalline structural changesand the guest encapsulation monitored by powder X-ray diffractionrevealed that a low sealed-heating temperature with a small amountof water was the optimal preparation condition for obtaining the HCform complex. The solution-state H-1 nuclear magnetic resonancemeasurement demonstrated that stoichiometric complexation was dependenton the cross-sectional area of the guest drug molecule. However, stoichiometriccomplexation could not be achieved with all guest drugs, and the encapsulationefficiency was found to be governed by the guest drug properties,such as vapor pressure and molecular size. The findings of this studywould contribute to understanding the complexation behavior of guestmolecules in multicomponent supramolecular complexes and offer newinsights into the fabrication of novel ordered supramolecular structures. A new sealed-heating condition is reportedto prepare theHC form of the drug/(PEG/& gamma;-CD-PPRX) complex. The guest drugin the HC form demonstrated a size-dependent stoichiometric complexation.The encapsulation efficiency of the guest drugs in the HC form complexwas governed by the vapor pressure and molecular size.