Cyclodextrin Derivatives Conjugated with Aromatic Moieties as pH-responsive Drug Carriers for Anthracycline

Abstract

The modification of cyclodextrins (CDs) with side chains containing aromatic groups was found to lead to an increase of the stability of the complex with the anticancer drug doxorubicin (Dox). The formation constants evaluated by voltammetry were several orders of magnitude larger than that of the unmodified β-CD ligand. For the CDs with aromatic moieties connected by linkers containing a triazole group, the formation constants of the complexes at pH 5.5 and 7.4 were very different. At lower pH, binding was much weaker as a result of protonation of the triazole moiety in the linker. The drug was then released from the complex. Molecular modeling of the Dox-β-CD system revealed different possible interactions between Dox and β-CD. The observed pH dependence of the complex formation constant can be exploited for drug delivery to the targeted cells. The toxicities of the synthesized complexes and each of the complex components were tested by the MTT assay on two cell lines, the human lung carcinoma and human cervical cancer cell lines.