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

• Published in: Journal of drug targeting Vol. 22; no. 7; pp. 658 - 668
• Main Authors: Kang, Sunyoung, Park, Euddeum, Kim, Youngeun, Lee, Seonju, Kwon, Jiwoong, Cho, Hyungdo, Lee, Yan
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 01.08.2014; Taylor & Francis
• Subjects: Acidic environment; Adamantane - chemistry; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - toxicity; beta-Cyclodextrins - chemistry; beta-Cyclodextrins - toxicity; Cell Survival - drug effects; cephradine; Cephradine - administration & dosage; Cephradine - toxicity; dimethylmaleic acid anhydride; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Carriers - toxicity; drug conjugation; Drug Liberation; Hydrogen-Ion Concentration; Maleic Anhydrides - chemistry; Mice; Molecular Structure; NIH 3T3 Cells; drug conjugation; cephradine; dimethylmaleic acid anhydride; Acidic environment
• ISSN: 1061-186X; 1029-2330
• DOI: 10.3109/1061186X.2014.928718

Abstract We developed a new pH-sensitive drug delivery carrier based on -cyclodextrin ( -CD) and 1-methyl-2-(2′-carboxyethyl) maleic anhydrides (MCM). The primary hydroxyl groups of -CD were successfully attached to MCM residues to produce a medusa-like -CD-MCM. The MCM residue was conjugated with cephradine (CP) with high efficiency ( > 90%). More importantly, -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 -CD-MCM-CP and the adamantane derivative was formed by simple mixing to show the possibility of introducing multi-functionality. Based on these results, -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.