betadex and maleic-acid

Two representative antibiotics, cephradine (CP) and moxifloxacin (MX), are covalently conjugated with a β-cyclodextrin (β-CD)-based carrier via pH-responsive 1-methyl-2-(2'-carboxyethyl) maleic acid amide (MCM) linkers with excellent conjugation efficiency via simple mixing. At pH 5.5, 90% and 80% of the CP and MX, respectively, are released from the carriers within 30 min, in contrast with the much-delayed release profile at pH 7.4. The in vitro inhibitory effect of β-CD-MCM-CP on the growth of Staphylococcus aureus is significantly lower than that of free CP at pH 7.4, but it reaches the level of free CP at pH 5.5. Moreover, S. aureus develops significant CP resistance after pretreatment with free CP, whereas the initial CP sensitivity is maintained after pretreatment with β-CD-MCM-CP at pH 7.4. However, β-CD-MCM-MX exhibits no such pH-responsive activity against Bacteroides fragilis, probably due to the insufficient stability of the MX conjugation at pH 7.4. In nondiabetic and diabetic mouse models, β-CD-MCM-CP significantly reduces the subcutaneous abscess scores and the bacterial counts in the abscess, although this represents only a marginal improvement in antimicrobial activity compared to free CP.

Topics: Amides; Animals; Anti-Bacterial Agents; Bacteria; beta-Cyclodextrins; Drug Carriers; Drug Liberation; Drug Resistance, Microbial; Hydrogen-Ion Concentration; Kinetics; Maleates; Mice; Microbial Sensitivity Tests; Models, Biological; Time Factors; Tissue Distribution

β-CD maleate (CDM) and β-CD itaconate (CDI) were prepared by esterification of β-cyclodextrin (β-CD) with maleic acid and itaconic acid using phosphate as a catalyst in a semi-dry process. The esterification of β-CD was carried out using [Itaconic acid ] or [Maleic acid ] 4 mol/mol of CD; M/L ratio 1:0.6; temperature 110 °C; [4-methoxyphenol] 2.5% amount of acid; reaction time 3.5h. The esterification rates of CDM and CDI are 70.38% and 21.02%, respectively. We found that CDM and CDI were both monoesters. Here, we also established a new evaluation method for the rate of esterification.

Topics: beta-Cyclodextrins; Esterification; Magnetic Resonance Spectroscopy; Maleates; Molecular Structure; Succinates; Thermogravimetry

(1)H NMR spectrometry, FT-IR spectroscopy, as well as molecular modeling at the AM1 level and normal mode analysis were used to characterise the interactions and the formation of inclusion complexes between three organic acids: maleic, fumaric, L-tartaric acids and betaCD. In aqueous medium, the complexation was confirmed by (1)H NMR spectroscopy using two-dimensional technique. The stable geometries of the complexes were determined by molecular modeling. Experimental infrared frequencies were assigned on the base of the vibrational normal mode calculation at the fully optimized geometry for the inclusion complexes. All the results point out the presence of stable inclusion complexes between acids and betaCD at the solid state. These results show the double role of the acid. Correlated with the theoretical and experimental data previously obtained for the miconazole/CD/acids complexes, in function of both acids and CDs structures, the acids can either stabilize the complexes by formation of a multicomponent complex or form acid/CD inclusion complexes, hindering the guest inclusion.

Topics: beta-Cyclodextrins; Dicarboxylic Acids; Fumarates; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Maleates; Miconazole; Models, Molecular; Pharmaceutical Vehicles; Spectroscopy, Fourier Transform Infrared; Tartrates; Thermodynamics

Poly(isobutene-alt-maleic acid)s modified with p-tert-butylphenyl or adamantyl groups interact with beta-cyclodextrin self-assembled monolayers (beta-CD SAMs) by inclusion of the hydrophobic substituents in the beta-cyclodextrin cavities. The adsorption was shown to be strong, specific, and irreversible. Even with a monovalent competitor in solution, adsorption to the beta-CD SAMs was observed, and desorption proved impossible. The adsorbed polymer layer was very thin as evidenced by surface plasmon resonance spectroscopy and AFM. Apparently, all or most hydrophobic groups of the polymers were employed efficiently in multivalent binding, as was further supported by the absence of specific binding of beta-CD-modified gold nanoparticles to the polymer surface assemblies. Supramolecular microcontact printing of the polymers onto the beta-CD SAMs led to assembly formation in the targeted areas of the substrates.

Topics: Alkenes; beta-Cyclodextrins; Hydrophobic and Hydrophilic Interactions; Maleates; Microscopy, Atomic Force; Molecular Structure; Polymers; Surface Plasmon Resonance