Acyclic Cucurbitnuril-type MolecularContainers: Influence of Aromatic Walls on their Function as SolubilizingExcipients for Insoluble Drugs

摘要

We studied the influence of the aromatic sidewalls on the ability of acyclic CB[n]-type molecular containers (>1a–>1e) to act as solubilizing agents for 19 insoluble drugs including the developmental anticancer agent PBS-1086. All five containers exhibit good water solubility and weak self-association (Ks ≤ 624 M^–1). We constructed phase solubility diagrams to extract Krel and Ka values for the container·drug complexes. The acyclic CB[n]-type containers generally display significantly higher Ka values than HP-β-CD toward drugs. Containers >1a–>1e bind the steroidal ring system and aromatic moieties of insoluble drugs. Compound >1b displays highest affinity toward most of the drugs studied. Containers >1a and >1b are broadly applicable and can be used to formulate a wider variety of insoluble drugs than was previously possible with cyclodextrin technology. For drugs that are solubilized by both HP-β-CD and >1a–>1e, lower concentrations of >1a–>1e are required to achieve identical [drug].