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

The supramolecular assembly between chlorhexidine and cyclomaltoheptaose (beta-cyclodextrin, betaCD) was characterized using NMR spectroscopy ((1)H, 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/betaCD 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).