Supramolecular self-assembly of β-cyclodextrin: an effective carrier of the antimicrobial agent chlorhexidine

• Published in: Carbohydrate research Vol. 342; no. 15; pp. 2286 - 2296
• Main Authors: Denadai, Ângelo M.L., Teixeira, Karina I., Santoro, Marcelo M., Pimenta, Adriano M.C., Cortés, Maria E., Sinisterra, Rubén D.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 05.11.2007
• Subjects: Actinobacillus - metabolism; Anti-Infective Agents, Local - administration & dosage; Anti-Infective Agents, Local - chemistry; Antimicrobial activity; beta-Cyclodextrins - chemistry; Calorimetry - methods; Chlorhexidine; Chlorhexidine - administration & dosage; Chlorhexidine - chemistry; Cyclomaltoheptaose; Drug Carriers; Drug Evaluation, Preclinical; Enterococcus faecalis - metabolism; Gels - chemistry; Kinetics; Magnetic Resonance Spectroscopy - methods; Mass Spectrometry - methods; Models, Chemical; Molecular Conformation; Spectrometry, Mass, Electrospray Ionization - methods; Supramolecular interactions; β-Cyclodextrin; β-Cyclodextrin; Antimicrobial activity; Chlorhexidine; Cyclomaltoheptaose; Supramolecular interactions
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/j.carres.2007.05.002

The supramolecular assembly between chlorhexidine and cyclomaltoheptaose (β-cyclodextrin, βCD) was characterized using NMR spectroscopy ( 1H, T 1, and ROESY), ESIMS and ITC. NMR data suggest the formation of high ordered complexes. ESIMS and ITC allowed the confirmation of the average stoichiometry as 1:4 and the thermodynamic data, also obtained by ITC, showed that the assembly is strongly stabilized by short distance interactions, but suffers a strong, opposite effect of entropy reduction. The antimicrobial activity of 1:1, 1:2, 1:3, and 1:4 Clx/βCD molar ratio mixtures was investigated in aqueous solution and after incorporation into mucoadhesive gels. These were used to determine the initial and the long-term antimicrobial activity, respectively, toward Actinobacillus actinomycetemcomitans ( A.a.) (Y4-FDC) and Enterococcus faecalis ( E.f.) (ATCC 14508) strains. The results showed that A.a. and E.f. were more susceptible to the 1:4 molar ratio mixture in either solution or gel ( p < 0.05).