Drug Development for Eradication with InclusionComplex of Multifunctional-modifiedβCD

抄録

We studied the properties of an inclusion complex of amoxicillin (AMPC) in a multifunctional-modified β-cyclodextrin (mf-βCD) having an affinity for bacteria. The mf-βCDs used were βCDs modified by the introduction, on the end of a hydrocarbon chain linker, of a saccharide or urea substituent group expected to have affinity for bacteria. Using quantum chemical methods, we showed that the use of mf-βCD stabilizes AMPC against acid, and that formation of an inclusion complex should produce bacterial affinity and improve bactericidal efficiency. The chemical stabilization of AMPC by mf-βCD was tested by hydrolysis. We also showed that in order to form a 1:1 complex of AMPC and mf-βCD (AMPC-mf-βCD) functioning as a drug delivery system (DDS), the optimal conditions require mixing mf-βCD with AMPC at a molar ratio between 1:5 and 1:10 (AMPC:mf-βCD). We used Gaussian program to determine the precedence of inclusion of AMPC by mf-βCDs and to obtain optimized structures of the complex. We demonstrated the importance of orbital interactions and electronic correlations during complexation for the emergence of chemotaxis in Helicobacter pylori¹⁾ toward the urea substituent on mf-βCDs. We further used the self-consistent reaction field (SCRF) method to study the effects of solvent. Using the optimized structures under solvent-free conditions, we calculated the energies of each AMPC-mf-βCD complex in water by the SCRF method using B3LYP/6-31G* levels.