A medusa-like β-cyclodextrin with 1-methyl-2-(2′-carboxyethyl) maleic anhydrides, a potential carrier for pH-sensitive drug delivery

Abstract

We developed a new pH-sensitive drug delivery carrier based on β-cyclodextrin (β-CD) and 1-methyl-2-(2′-carboxyethyl) maleic anhydrides (MCM). The primary hydroxyl groups of β-CD were successfully attached to MCM residues to produce a medusa-like β-CD–MCM. The MCM residue was conjugated with cephradine (CP) with high efficiency ( > 90%). More importantly, β-CD–MCM–CP responded to the small pH drop from 7.4 to 5.5 and released greater than 80% of the drugs within 0.5 h at pH 5.5. In addition, the inclusion complex between β-CD–MCM–CP and the adamantane derivative was formed by simple mixing to show the possibility of introducing multi-functionality. Based on these results, β-CD–MCM can target weakly acidic tissues or organelles, such as tumours, inflammatory tissues, abscesses or endosomes, and be easily modified with various functional moieties, such as ligands for cell binding or penetration, enabling more efficient and specific drug delivery.

• Acidic environment
• cephradine
• dimethylmaleic acid anhydride
• drug conjugation

Acknowledgements

This paper is dedicated to my respectable mentor, Prof Kazunori Kataoka.