CYCLODEXTRIN INCLUSION COMPLEXES OF PHARMACEUTICALLY ACTIVE DERIVATIVES OF THE CYTISINE ALKALOID AND THEIR HEMORHEOLOGICAL ACTIVITY

The alkaloid cytisine is of great importance for modern pharmacological studies. This alkaloid can be used as a component of the supramolecular system with cyclic oligosaccharides, namely β-cyclodextrins, which have a truncated cone-shaped molecule with internal protons Н3 and Н5 and external ones Н2 and Н4. The aim of the work is to obtain inclusion complexes of pharmaceutically active derivatives of the alkaloid cytisine. The inclusion complexes of cytisine alkaloid derivatives with β-CD and 2-HP-β-CD were obtained by the coprecipitation method. Thermogravimetric, differential thermal, and differential scanning calorimetric analyzes were performed. It was shown that inclusion complexes of substrate with cyclodextrin cavity of receptors were formed. The greatest change in the chemical shifts of protons during the formation of supra-molecular complexes occurs with the internal protons H-3 and H-5 of the cyclodextrin cavity. All calculated values are in good agreement with experimental data. The prepa-ration of supramolecular complexes has been proven using a variety of physicochemical methods of analysis. According to DSC data, the process of complexes destruction in the temperature range of 30-610°C was studied in comparison with the data of the initial cyclodextrin. The hemorheological effects of the investigated samples were studied in vitro. Among four samples studied, two samples showed the ability to reduce blood viscosity in vitro in the blood hyperviscosity model.

Enhanced Stability and Bioactivity of Natural Anticancer Topoisomerase I Inhibitors through Cyclodextrin Complexation

The use of cyclodextrins as drug nano-carrier systems for drug delivery is gaining importance in the pharmaceutical industry due to the interesting pharmacokinetic properties of the resulting inclusion complexes. In the present work, complexes of the anti-cancer alkaloids camptothecin and luotonin A have been prepared with β-cyclodextrin and hydroxypropyl-β-cyclodextrin. These cyclodextrin complexes were characterized by nuclear magnetic resonance spectroscopy (NMR). The variations in the 1H-NMR and 13C-NMR chemical shifts allowed to establish the inclusion modes of the compounds into the cyclodextrin cavities, which were supported by docking and molecular dynamics studies. The efficiency of the complexation was quantified by UV-Vis spectrophotometry and spectrofluorimetry, which showed that the protonation equilibria of camptothecin and luotonin A were drastically hampered upon formation of the inclusion complexes. The stabilization of camptothecin towards hydrolysis inside the cyclodextrin cavity was verified by the quantitation of the active lactone form by reverse phase liquid chromatography fluorimetric detection, both in basic conditions and in the presence of serum albumin. The antitumor activity of luotonin A and camptothecin complexes were studied in several cancer cell lines (breast, lung, hepatic carcinoma, ovarian carcinoma and human neuroblastoma) and an enhanced activity was found compared to the free alkaloids, particularly in the case of hydroxypropyl-β-cyclodextrin derivatives. This result shows that the cyclodextrin inclusion strategy has much potential towards reaching the goal of employing luotonin A or its analogues as stable analogues of camptothecin.

The thermodynamic study of p-methoxycinnamic acid inclusion complex formation, using β-cyclodextrin and hydroxypropyl-β-cyclodextrin

Objectives Cyclodextrin’s ability to form an inclusion complex with a guest molecule is a function of two factors. The first is steric and depends on the relative size of cyclodextrin cavity to the guest molecule, while the second is the thermodynamic interaction between the different system components. This study therefore aims to determine the effect of β-cyclodextrin and hydroxypropyl-β-cyclodextrin as complex formers, on thermodynamic parameter values (ΔH, ΔG, and ΔS) in the formation of inclusion complex with p-methoxycinnamic acid (pMCA). Methods The pMCA complex formation with β-cyclodextrin or hydroxypropyl-β-cyclodextrin was determined in 0.02 pH 4.0 M acetate buffer and 0.02 M pH 7.0 phosphate buffer, with a 0.2 µ value at 32, 37, and 42 ± 0.5 °C. This experiment was carried out in a waterbath shaker until a saturated solution was obtained. Subsequently, pMCA concentration was determined using UV spectrophotometer at the maximum pMCA wavelength, at each pH. Results The result showed pMCA formed inclusion complex with β-cyclodextrin or hydroxypropyl-β-cyclodextrin and exhibited increased solubility with increase in β-cyclodextrin or hydroxypropyl-β-cyclodextrin concentration. This temperature rise led to a decrease in the complex’s constant stability (K). Furthermore, the interaction showed a negative enthalpy (∆H<0) and is a spontaneous processes (∆G<0). At pH 4.0, an increase in the system’s entropy occurred (∆S>0), however, at pH 7.0, the system’s entropy decreased (∆S<0). Conclusions The rise in pMCA solubility with increase in cyclodextrin solution concentration indicates an inclusion complex has been formed, and is supported by thermodynamic data.

Synthesis, Characterization and Antibacterial Activity of Novel β-Cyclodextrin Polyurethane Materials

The advanced water treatment taken by organic micro-pollution or microbiological pollution water resource has been a hot issue of public concern. In this article, a novel quaternary ammonium salt functionalized β-cyclodextrin polyurethane (QAS-β-CDPU) was successfully constructed for above-mentioned pollutants removal. By adjusting the proportion of the chlorine-containing monomers, we studied the effect of different quaternization degree (0%, 20%, 40%, 60%) on solvent resistance and thermal stability. Staphylococcus aureus are recognized as significant human bacterial pathogens, which were used as model bacteria to investigate the antibacterial activity by contact-killing tests. Methylene blue (MB) served as a toxic organic model to quantify the dye wastewater remediation efficiency. Research shows that the reaction of β-cyclodextrin and diisocyanate can form a cyclodextrin-based carbamate network structure. Since both the cyclodextrin cavity and the carbamate network may remove the dye, the obtained polymer has a double advantage. Besides, the presence of quaternary ammonium groups enables QAS-β-CDPU to possess good bactericidal properties. When the quaternization degree is 60%, sterilization rate of QAS-β-CDPU comes to 97.3%. On basis of this simple, green and economical synthetic route, QAS-β-CDPU has the potential to become an ideal multifunctional material in water purification.

ENCAPSULATION OF VITAMIN AEVIT OIL SOLUTION WITH β-CYCLODEXTRIN

The present work aimed at encapsulation of fat-soluble vitamin Aevit (vitamins A and E, oil) with β-cyclodextrin. Inclusion complex of vitamins A and E with β-cyclodextrin was prepared in an aqueous alcohol medium by ultrasonic treatment. The surface morphology of the resulting clathrate inclusion complexes was described using a scanning electron microscope. The results of thermographic measurements on a differential scanning calorimeter are presented. The spectral properties of the inclusion complex are characterized by 1H and 13C NMR spectroscopy data. The experimental results confirmed the existence of a complex of inclusion of β-cyclodextrin with vitamin Aevit (2:1). The activation energy of the thermooxidation destruction reaction of the clathrate complex β-cyclodextrin:vitamin Aevit was calculated, kinetic parameters of thermal destruction of clathrate were determined. These parameters were determined based on the Freeman-Carroll, Sharpe-Wentworth, Ahar and Coates-Redfern methods. The use of the above models made it possible to graphically establish the thermodynamic parameters of the thermal decomposition of β-cyclodextrin and its clathrate with vitamin. The data of thermographic measurements on a differential scanning calorimeter showed that the thermal destruction of the Aevite clathrate with β-cyclodextrin begins with the removal of water molecules from the β-cyclodextrin cavity, then the “guest” substance and the cyclic oligosaccharide are destroyed.