Soluble Β-cyclodextrin Polymer Research Articles

Preparation and evaluation of a functional effervescent powder based on inclusion complexes of orange oil and β-cyclodextrin derivatives

Flavoured functional effervescent powders are becoming increasingly popular by consumers due to their health benefits and easy dissolution. In present study, orange flavoured effervescent powders having functional properties were prepared. Orange oil (O) was blended with different essential oils (EOs) that have high antioxidant activity. The orange oil and the O-EOs blends were subjected to odour sensory evaluation, gas chromatography-mass spectrometry (GC-MS) analysis and evaluation of radical scavenging activity. Combinations of two water soluble β-cyclodextrin polymers, 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) and epichlorohydrin-β-cyclodextrin (EPI-β-CD), were prepared at different molar ratios (3:1 and 1:3, F1 and F2, respectively). The O-EOs blends that showed the highest antioxidant activities and best odour qualities were encapsulated with F1 and F2, separately. The orange flavoured inclusion complexes were prepared by freeze drying method. The particle sizes of the inclusion complex powders were in the nanoscale. Characterization of the inclusion complexes nanoparticles was performed by scanning electron microscopy (SEM), and fourier transform infrared microscopy (FT-IR). The results confirmed the successful formation of the inclusion complexes. However, inclusion complex of O-EOs (300 mg) blend with F1 (OF1cIC) showed the smallest particle size (113.90±15.90 nm), the more negative zeta potential (−27.10±1.27 mV), the highest encapsulation efficiency (95.51%) and best odour quality. Therefore, it was mixed with an effervescent powder having high acceptable characteristics. The orange flavoured effervescent powder showed superior flowability.

Cyclodextrin Nanoparticles Bearing 8-Hydroxyquinoline Ligands as Multifunctional Biomaterials.

Cyclodextrins are used as building blocks for the development of a host of polymeric biomaterials. The cyclodextrin polymers have found numerous applications as they exhibit unique features such as mechanical properties, stimuli responsiveness and drug loading ability. Notwithstanding the abundance of cyclodextrin polymers studied, metal-chelating polymers based on cyclodextrins have been poorly explored. Herein we report the synthesis and the characterization of the first metal-chelating β-cyclodextrin polymer bearing 8-hydroxyquinoline ligands. The metal ions (Cu2+ or Zn2+ ) can modulate the assembly of the polymer nanoparticles. Moreover, the protective activity of the new chelating polymer against self- and metal-induced Aβ aggregation and free radical species are significantly higher than those of the parent compounds. These synergistic effects suggest that the incorporation of hydroxyquinoline moieties into a soluble β-cyclodextrin polymer could represent a promising strategy to design multifunctional biomaterials.

Endocytosis of fluorescent cyclodextrins by intestinal Caco-2 cells and its role in paclitaxel drug delivery

Cyclodextrins are widely used excipients in pharmaceutical formulations. They are mainly utilized as solubilizers and absorption enhancers, but recent results revealed their effects on cell membranes and pharmacological barriers. In addition to the growing knowledge on their interaction with plasma membranes, it was confirmed that cyclodextrins are able to enter cells by endocytosis. The number of the tested cyclodextrins was limited, and the role of this mechanism in drug absorption and delivery is not known. Our aim was to examine the endocytosis of fluorescently labeled hydroxypropyl-β-cyclodextrin, random methyl-β-cyclodextrin and soluble β-cyclodextrin polymer, and the cellular uptake of the fluorescent paclitaxel derivative-random methyl-β-cyclodextrin complex. The studied cyclodextrin derivatives were able to enter Caco-2 intestinal cells and localized in vesicles in the cytoplasm, while their permeability was very limited through Caco-2 monolayers. We demonstrated for the first time that the fluorescent paclitaxel derivative and rhodamine-labeled random methyl-β-cyclodextrin were detected in the same intracellular vesicles after treating cells with their inclusion complex. These results indicate that the endocytosis of cyclodextrin complexes can contribute to drug absorption processes.

A new inclusion complex of amlodipine besylate and soluble β-cyclodextrin polymer: preparation, characterization and dissolution profile

Amlodipine besylate (AML) has become the most popular blood pressure medication for hypertensive pets. It belongs to the class I (high solubility and high permeability) according to BCS and is marketed in Europe only as white tablets equivalent to 2.5, 5.0 and 10.0 mg of amlodipine for oral administration. Unfortunately, oral AML dosage for cats and dogs is in the range 0.1–0.2 and 0.625–0.125 mg/kg/die respectively. Moreover, AML shows a slight solubility in water according to Ph. Eur. 7°. According to these considerations, the aim of this work was the complexation between soluble β-cyclodextrin polymer (CD) and AML using the solubilization/freeze-dried method to obtain powders easily dosable and soluble in water for the treatment of hypertension in pets. The complex in solution was evaluated by phase solubility studies that indicated the optimal 2:1 drug/CD ratio to form a stable complex. UV–Vis absorption and circular dichroism showed the formation of a complex with a weak bond such as confirmed by differential scanning calorimetry, infrared spectroscopy and fluorescence microscopy. In vitro dissolution/release tests were performed in water to investigate the influence of formulative parameters on drug dissolution/release properties. The inclusion of AML in CD increased its wettability, dissolution rate and solubility in water. This method could be a suitable approach for the administration of an extemporaneous solution of the antihypertensive drug to guarantee a correct dose to pets increasing the compliance.

Association of poly- N-[tris(hydroxymethyl)methyl] acrylamide with a water soluble β-cyclodextrin polymer

An acrylic polymer with pendent adamantyl groups was synthesized and its properties in an aqueous solution with a β-cyclodextrin (βCD) epichlorhydrin polymer examined. Viscosity properties of precursor and modified polymers show differences at low concentrations, but not at higher concentration probably due to very important hydrogen bonds which prevent the formation of intermolecular hydrophobic bonds. The association of both complementary polymers through the inclusion of adamantyl groups is evidenced by phases separation occurrence. Phase diagrams were established at two different concentrations of polymers. We have shown a maximal association of both polymers at these two concentrations, for the same ratio βCD moles/adamantyl groups: 2.4. Salt addition favors this association and displaces the two phases zone to smaller concentrations of modified polymer. Further, 4-nitrophenol can be extracted by the concentrated phase resulting from mixture of solutions of guest and host polymers, pointing out the availability of the associated phase to trap organic molecules.

Association of hydrophobically modified poly ( N, N-dimethylacrylamide hydroxyethylmethacrylate) with water soluble β-cyclodextrin polymers

Hydrophobically associating polymers have been obtained by chemical modification of poly ( N, N-dimethyl acrylamide hydroxyethylmethacrylate) consisting in the introduction of adamantyl groups (Ad). Viscosity studies of dilute solutions of modified polymers show lower reduced viscosities than precursor solutions attributed to intramolecular hydrophobic associations. At higher concentrations intermolecular associations take place. In all cases, the viscosities are of limited value. Hydrophobic microdomains were evidenced by static fluorescence measurements in the presence of pyrene and critical aggregation concentrations determined. A study of fluorescence versus temperature has shown a modification of hydrophobic properties above 40°C corresponding to a coiling of the molecules, masking the hydrophobic groups. When these modified polymers are added to solutions of β-cyclodextrin epichlorhydrin polymer (βCD/EP), associations take place between the two polymers due to inclusion of adamantyl groups in cyclodextrin cavities. High viscosity enhancements are observed which are maximum for a precise composition of both polymers. This composition corresponds to the stoechiometry 1 adamantyl group for 1 CD cavity and varies with molecular weight and hydrophobe content of the modified polymer. Associative phase diagrams were stated which confirm the strong association of both polymers via inclusion of adamantyl groups in the β-cyclodextrin cavities.

Preparation and characterization of water soluble high molecular weight β-cyclodextrin-epichlorohydrin polymers

Water soluble β-cyclodextrin polymers were prepared from β-cyclodextrin crosslinked with epichlorohydrin under basic conditions. The influence of preparation conditions on the molecular weight distribution has been investigated. The knowledge of this relationship allows for the choice of reaction parameters according to the desired weight distribution of the β-cyclodextrin polymer. A procedure was developed for the preparation of high molecular weight water soluble polymer ( Mw higher than 10 4).

Enantiomeric separation by capillary electrophoresis using a soluble neutral β-cyclodextrin polymer

Enantiomers of several racemic basic compounds of pharmaceutical interest and three tryptophan derivatives were investigated by capillary electrophoresis employing a soluble β-cyclodextrin polymer and native β-cyclodextrin. The effects of the concentration of the polymer added to the background electrolyte and of the pH of the buffer on the effective mobility and resolution of the studied compounds were examined. The β-cyclodextrin polymer showed a higher stereoselectivity than the parent β-cyclodextrin. Enantionselectivity and resolution were influenced by the concentration of the β-cyclodextrin polymer and the background electrolyte. A pH study, carried out in the pH range 2.7–6, showed that an increase in pH caused a general decrease in both resolution and selectivity. The best results for the enantiomeric separation of the basic compounds studied were obtained at pH 2.7.

Interaction of nonylphenyl and tributylphenyl ethylene oxide ionic surfactants with highly soluble cyclodextrin derivatives

The modification of the hydrophobicity of some ethoxylated nonylphenol and tributylphenol surfactants with various soluble β-cyclodextrin polymers has been studied by reversed-phase chromatography. Stepwise regression analysis proved that the complex forming capacity of surfactants decreases with increasing diameter of the hydrophobic moiety of surfactants, the properties of the crosslinking agent used for preparation of the polymers has no significant effect on the host-guest interaction, the presence of carboxyl groups in the polymer considerably improved the complex stability.

Charge-transfer chromatographic study on the inclusion complex formation of some barbituric acid derivatives with varrious cyclodextrins

The inclusion complexing capacity of 21 barbituric acid derivatives with α-, β- and γ-cyclodextrins, with a water soluble β-cyclodextrin polymer and with 2,6-di-O-methyl-β-cyclodextrin was determined by chargetransfer chromatography on reversed-phase thin-layer plates. It was established that 2,6-di-O-methyl-β-cyclodextrin formed the most stable complexes with the barbituric acid derivatives followed by the water soluble β-cyclodextrin polymer. The complex forming capacities of β- and γ-cyclodextrins were similar to each other while the α-cyclodextrin formed very weak complexes. Each cyclodextrin had a different sterical requirement of substituents of the barbituric acid derivatives to fit optimally into the cyclodextrin cavity.

Reversed-phase thin-layer chromatography of some chlorophenols in the presence of a soluble β-cyclodextrin polymer

Reversed-phase thin-layer chromatography of some chlorophenols in the presence of a soluble β-cyclodextrin polymer

Reversed-phase thin-layer chromatography of barbiturates in the presence of soluble β-cyclodextrin polymer

Reversed-phase thin-layer chromatography of barbiturates in the presence of soluble β-cyclodextrin polymer