Β-cyclodextrin Molecules Research Articles

Preparation, characterization and in vivo evaluation of formulation of repaglinide with hydroxypropyl-β-cyclodextrin

The therapeutic efficacy of repaglinide (RPG) is limited by the low and variable oral bioavailability owing to its limited aqueous solubility. In our present study, the development and evaluation of inclusion complex applying hydroxypropyl-β-cyclodextrin (HP-β-CD) for the improvement of oral bioavailability of repaglinide was investigated systematically. The inclusion complex of repaglinide was prepared by lyophilization technique using drug: hydroxypropyl-β-cyclodextrin (1:15 mole). The prepared complexation was characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), NMR spectroscopy and evaluated by dissolution studies. The 1H NMR was used in the structure study of repaglinide-HP-β-CD (RPG-HP-β-CD) inclusion complex. The analysis proved the higher probability of the repaglinide A-ring into the narrow rim of the β-cyclodextrin molecule. All the characterization information confirmed the formation of RPG-HP-β-CD inclusion complex. The in vivo pharmacokinetics of RPG-HP-β-CD and their physical mixture were performed in beagle dogs. For the first time, a simple, rapid, and sensitive LC–MS/MS method for determination of RPG in beagle dog plasma was developed. The Cmax and AUC0−t of RPG-HP-β-CD were 2.5 and 2 times higher than that of the physical mixture. These results suggested that the interaction of repaglinide with HP-β-CD could notably improve the dissolution rate and bioavailability of repaglinide comparing with its physical mixture.

Study on quantitative mechanism and the interference of the UV spectrum of HABS reduced by β-Cyclodextrin

A novel ultraviolet absorption spectrometry method was developed for the quantitative determination of HABS by adding β-cyclodextrin with the molar ratio of 1:1 in strong interference aqueous solution. The results indicated that the effect of several common interfering flooding agents (SAS, OP-10, HPAM) on the determination of HABS could be greatly reduced in β- cyclodextrin aqueous solution. Thus, the determination errors of the determined HABS were less than 2.0% under strong inter- ference, and the detection limit (S/N==3) of the method could be also as high was 8.3-9.1 x 10(-4) mg · L(-1). Various characterization results including 1H-NMR, TG-DSC and FTIR showed the interaction between β-cyclodextrin and HABS. The results of H-NMR analysis showed that HABS molecule could enter into the interior of the cavity of β-cyclodextrin molecule. TG-DSC analysis exhibited that the stable inclusion of β-cyclodextrin and HABS could be automatically formed. The interactions between the functional groups of β-cyclodextrin and HABS were showed by FTIR analysis, which also exhibited that the stable inclusion could be formed by HABS entering from the narrow or the broad mouth of the β-cyclodextrin. The interference of the UV spectrum of HABS could be reduced by β-cyclodextrin since the interaction between β-cyclodextrin due to the interaction between β-cyclodextrin and HABS in the inclusion complex.

Fabrication of a photocontrolled surface with switchable wettability based on host-guest inclusion complexation and protein resistance.

A novel surface-modification strategy has been developed for the construction of a photocontrolled silicon wafer surface with switchable wettability based on host-guest inclusion complexation. The silicon wafer was first modified by guest molecule azobenzene (Azo) via a silanization reaction. Subsequently, a series of polymers with different polarities were attached to host molecule β-cyclodextrin (β-CD) to prepare β-CD-containing hemitelechelic polymers via click chemistry. Finally, a photocontrolled silicon wafer surface modified with polymers was fabricated by inclusion complexation between β-CD and Azo, and the surface properties of the substrate are dependent on the polymers we used. The elemental composition, surface morphology, and hydrophilic/hydrophobic property of the modified surfaces were characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscope, and contact angle measurements, respectively. The antifouling property of the PEG-functionalized surface was evaluated by a protein adsorption assay using bovine serum albumin, which was also characterized by XPS. The results demonstrate that the surface modified with PEG possesses good protein-resistant properties.

A Novel Synthesis of Monodispersed Magnetite Nanoparticles by an Organometallic Complexed Precursor

Monodispersed magnetite (Fe3O4) nanoparticles were obtained via an innovative three step synthetic approach. First, the formation of iron enneacarbonyl, Fe2(CO)9, a stable, solid organometallic complex compound, took place in a hexane solution, by the decomposition reaction of the unstable, liquid iron pentacarbonyl, Fe (CO)5, in the presence of sunlight and mild heating. In a second step, the dry compound Fe2(CO)9 was complexed with β-Cyclodextrin (β-CD) molecules, according to a combination of two modified complexation procedures. Steric hindrance of the organometallic molecules was achieved, among the interstices of the formed CD molecular network, which poses a novel, very crucial size control factor and stabilizing agent for the synthesized nanoparticles.

A Novel Approach for the Synthesis of PEGylated Monodispersed Superparamagnetic Iron Oxide Nanoparticles

PEGylated, monodispersed, superparamagnetic, iron oxide nanoparticles (Fe3O4 / γ-Fe2O3) were synthesized by using a novel metal-organic approach in three steps. Ferric nitrate nonahydrate, Fe (NO3)3.9H2O, was used as iron source, which was sterically hindered among the interstices and / or in the cavities of β-Cyclodextrin (β-CD) molecules, following a modified complexation procedure. Via a polyol process the obtained complex system was first dispersed in polyethylene glycol (PEG) and under mild thermal treatment and in the presence of 1,12 dodecanediol, a new complex system of carboxylate type was formed, between ferric nitrate and PEG, denoted Fe (NO3)3.9H2O-PEG. This metal-organic precursor was thermally decomposed, forming the iron oxide nanoparticles. The obtained particles were characterized by X-ray diffraction spectroscopy (XRD), Fourier Transform Infrared spectroscopy (FTIR) and transmission electron microscopy (TEM).

Nanoporous functional organosilicas for sorption of toxic ions

The chemical immobilization of β-cyclodextrin and its bromoacetyl and thiosemicarbazidoacetyl functional derivatives on the surface of highly disperse amorphous nanoporous silica was performed. β-Cyclodextrin-containing silicas were found to have high affinity to mercury(II), cadmium(II), and zinc(II) cations. Supramolecular surface structures formed whose chemical composition depends on the nature of the sorbed cations and the functional substituents in the attached β-cyclodextrin molecules.

Functional materials from the covalent modification of reduced graphene oxide and β-cyclodextrin as a drug delivery carrier

We report a drug delivery system based on the covalently reduced graphene oxide (rGO) with p-aminobenzoic acid (rGO-C6H4-COOH) for the loading and targeted delivery of the anticancer drug, doxorubicin (DOX). The colloidal solution of rGO-C6H4-COOH conjugated by polyethyleneimine (PEI) and Biotin was prepared. This endows the colloidal solution of rGO-C6H4-CO-NH-PEI-NH-CO-Biotin, which presents excellent water-solubility and targeting as a drug delivery system. β-Cyclodextrin (β-CD) molecules, which are host molecules for accommodating guest molecules, such as water insoluble anticancer drugs, were introduced to reduce the cytotoxicity of the drug delivery system and to improve the biocompatibility. The drug delivery of rGO-C6H4-CO-NH-PEI-NH-CO-CD-Biotin has a ∼24.64% drug (DOX) loading ratio. The drug release behavior was pH dependent at higher DOX concentrations, but salt dependent at lower DOX concentrations, which could be exploited for controlled drug release in cancer cells. The DOX loaded on rGO-C6H4-CO-NH-PEI-NH-CO-CD-Biotin could effectively induce HepG2 cancer cell apoptosis. This can be explained by the conjugation of DOX and rGO-C6H4-CO-NH-PEI-NH-CO-CD-Biotin being able to arrest the cancer cells in the G2 phase, which is the most sensitive to the anticancer drug.

Control the Wettability of Poly(N-isopropylacrylamide-co-1-adamantan-1-ylmethyl acrylate) Modified Surfaces: The More Ada, the Bigger Impact?

Surface-initiated SET-LRP was used to synthesize polymer brush containing N-isopropylacrylamide and adamantyl acrylate using Cu(I)Cl/Me6-TREN as precursor catalyst and isopropanol/H2O as solvent. Different reaction conditions were explored to investigate the influence of different parameters (reaction time, catalyst concentration, monomer concentration) on the polymerization. Copolymers with variable 1-adamantan-1-ylmethyl acrylate (Ada) content and comparable thickness were synthesized onto silicon surfaces. Furthermore, the hydrophilic and bioactive molecule β-cyclodextrin-(mannose)7 (CDm) was synthesized and complexed with adamantane via host-guest interaction. The effect of adamantane alone and the effect of CDm together with adamantane on the wettability and thermoresponsive property of surface were investigated in detail. Experimental and molecular structure analysis showed that Ada at certain content together with CDm has the greatest impact on surface wettability. When Ada content was high (20%), copolymer-CDm surfaces showed almost no CDm complexed with Ada as the result of steric hindrance.

A novel FRET-based fluorescent chemosensor of β-cyclodextrin derivative for TNT detection in aqueous solution

A new fluorescent sensor based on single water-soluble β-cyclodextrin (β-CD) molecule as the support carrier of donor and acceptor complex was designed, and used for TNT detection by fluorescence resonance energy transfer (FRET). In this sensing platform, per-6-amino-β-CD (per-6-NH2-β-CD) was used as the detection vehicle. The probe dye of fluorescein 5(6)-isothiocyanate (FITC) was covalently linked onto the per-6-NH2-β-CD rim with the grafting molar ratio of 1:1, the residual amino groups of per-6-NH2-β-CD can adsorb TNT molecules by forming Meisenheimer complex (TNT–amine complex) with TNT. The absorbtion spectrum of this complex has a spectral overlapping with the emission of FITC in aqueous solution, so it can strongly suppress the fluorescence emission of the adjacent FITC through FRET on β-CD vehicle. This FRET-based fluorescent sensing technique provides a facile, ultrasensitive and selective detection method for TNT molecule. The observed linear fluorescence intensity change could allow the quantitative detection TNT with the detection limit of 20nM in water.

Cyclodextrin/Paclitaxel Complex in Biodegradable Capsules for Breast Cancer Treatment

A novel type of biocompatible hollow capsules that combine severable favorable features as a hydrophobic drug carrier, including host–guest complexation in the shell, the unique biological functions of hyaluronic acid (HA), and transport properties of the multilayer shell, was designed and prepared. These capsules were generated by layer-by-layer (LbL) deposition of HA modified with β-cyclodextrin (CD) molecules and poly(l-lysine) (PLL) on calcium carbonate particles. Simultaneously, paclitaxel (PTX) was loaded in the LbL wall via host–guest interaction. Under physiological conditions, the incorporated anticancer drug was slowly released, and the capsules remained stable. Because the PTX molecules are selectively complexed by CD in the shell, their release can be triggered by the addition of competitive cyclodextrin molecules in the external medium. By incubating the capsules with breast cancer cells (MDA-MB-231), it was found that the cells bound specifically to the capsules through the CD44 receptor of ...

Activation of snap-top capped mesoporous silica nanocontainers using two near-infrared photons.

Photoactivation of "snap-top" stoppers over the pore openings of mesoporous silica nanoparticles releases intact cargo molecules from the pores. The on-command release can be stimulated by either one UV photon or two coherent near-IR photons. Two-photon activation is particularly desirable for use in biological systems because it enables good tissue penetration and precise spatial control. Stoppers were assembled by first binding photolabile coumarin-based molecules to the nanoparticle surface. Then, after the particles were loaded with cargo, bulky β-cyclodextrin (CD) molecules were noncovalently associated with the substituted coumarin molecule, blocking the pores and preventing the cargo from escaping. One-photon excitation at 376 nm or two-photon excitation at 800 nm cleaves the bond holding the coumarin to the nanopore, releasing both the CD cap and the cargo. The dynamics of both the cleavage of the cap and the cargo release was monitored using fluorescence spectroscopy. This system traps intact cargo molecules without the necessity of chemical modification, releases them with tissue-penetrating near-IR light, and has possible applications in photostimulated drug delivery.

Analysis of Binding Properties Between β-Cyclodextrin Bipyridine-ruthenium Derivative and Vitamins by Their Fluorescence Spectra

This paper presents a research of the binding interaction of a new synthetized β-cyclodextrin bipyridine-ruthenium derivative[β-CD-Ru(bpy)3] with a series of vitamins using fluorescent spectrometry.The performance of fluorescence emission of β-CD-Ru(bpy)3 was excellent due to the existence of the center of bipyridine-ruthenium.Based on the effect of molecular recognition between β-cyclodextrin and guest molecule,the fluorescence quenching occured because of the energy transfer between the β-CD-Ru(bpy)3 and the vitamin when a kind of vitamin was added.According to the quantitative value of fluorescence quenching,the binding constants of the new derivative with respect to various vitamins were determined by Benesi-Hildebrand Equation.The results show that the binding capacities of the vitamins with β-CD-Ru(bpy)3 were in a descending sequence of VB12VK3VCVA.

Adamantyl-terminated dendronized molecules: synthesis and interaction with β-cyclodextrin-functionalized poly(dimethylsiloxane) interface

The supramolecular interaction between the host molecule β-cyclodextrin (β-CD) and the guest molecule adamantane is extensively applied in several disciplines. However, recent studies on the applications of this molecular recognition mainly focused on glass, silicon, and gold substrates. Few studies have explored the field of poly(dimethylsiloxane) (PDMS), an optically transparent elastomer widely used in biological microfluidic devices. In the present study, various functional group-modified adamantyl-terminated dendronized molecules were synthesized via an efficient and facile route. The binding of adamantyl-terminated dendronized molecules onto β-CD-conjugated PDMS surfaces and their reversible dissociation from PDMS surfaces through the competitive mechanism of β-CD-N3 were studied. The results showed that the dissociation is relatively slow compared with the binding, and the former process can be accelerated through exchanging the original β-CD-N3 solution with a fresh one. Afterward, more complex multilayer assemblies were constructed on PDMS surfaces using the host–guest interaction between adamantane and β-CD as well as between biotin and streptavidin. A further study on the association and dissociation of the established multilayer assemblies showed that the assembly constructed with a biotinylated monoadamantyl-terminated molecule has a reversible property, whereas that with a biotinylated triadamantyl-terminated molecule has an irreversible property. These results demonstrated that the reversible properties of the fabricated assembly can be easily modulated on the PDMS surfaces by regulating the valence of the supramolecular interaction between adamantane and β-CD.

Simultaneous detection of CMPA and PMPA, hydrolytes of soman and cyclosarin nerve agents, by nanopore analysis

A sensitive nanopore-based analytical method was developed for the detection of cyclohexyl methylphosphonic acid (CMPA) and pinacolyl methylphosphonate (PMPA), hydrolytes of nerve agents soman and cyclosarin, respectively. The method uses a multi-functionalized α-hemolysin protein ion channel as the sensing element, with a host molecule β-cyclodextrin lodged in the lumen of the channel as a molecular adapter. The capture and release of CMPA/PMPA by the β-cyclodextrin host caused current modulations in the nanopore. Since the event residence times and amplitudes were significantly different, CMPA and PMPA could conveniently be differentiated and simultaneously quantitated.

Determination of the Absolute Configuration of Aegelinol by Crystallization of Its Inclusion Complex with β-Cyclodextrin

The absolute configuration and structure of aegelinol, a pyranocoumarin isolated from Ferulago asparagifolia Boiss (Apiaceae), has been determined by crystallography. Crystal structure of the inclusion complex of aegelinol in β-cyclodextrin was determined (a = 15.404(1) Å, b = 15.281(1) Å, c = 17.890(1) Å, α = 99.662(1), β = 113.4230(1), γ = 102.481(1)°, P1; R1 = 6.71%) and allowed unambiguous determination of the absolute configuration of the stereogenic center of aegelinol. The pyranocoumarin guest is included within the cylindrical cavity formed by dimeric β-cyclodextrin molecules with a head-to-head arrangement. Crystal structure of aegelinol alone was also determined (a = 6.8921(3) Å, b = 11.4302(9) Å, c = 44.964(3) Å, P212121; R1 = 4.44%) and allowed precise determination of its geometry. Aegelinol crystallizes with three molecules in the asymmetric unit held together by H-bonds and π-stacking interactions.

A Versatile Multicomponent Assembly via β‐cyclodextrin Host–Guest Chemistry on Graphene for Biomedical Applications

A multi-component nanosystem based on graphene and comprising individual cyclodextrins at its surface is assembled, creating hybrid structures enabling new and important functionalities: optical imaging, drug storage, and cell targeting for medical diagnosis and treatment. These nanohybrids are part of a universal system of interchangeable units, capable of mutilple functionalities. The surface components, made of individual β-cyclodextrin molecules, are the "hosts" for functional units, which may be used as imaging agents, for anti-cancer drug delivery, and as tumor-specific ligands. Specifically, individual β-cyclodextrin (β-CD), with a known capability to host various molecules, is considered a module unit that is assembled onto graphene nanosheet (GNS). The cyclodextrin-functionalized graphene nanosheet (GNS/β-CD) enables "host-guest" chemistry between the nanohybrid and functional "payloads". The structure, composition, and morphology of the graphene nanosheet hybrid have been investigated. The nanohybrid, GNS/β-CD, is highly dispersive in various physiological solutions, reflecting the high biostability of cyclodextrin. Regarding the host capability, the nanohybrid is fully capable of selectively accommodating various biological and functional agents in a controlled fashion, including the antivirus drug amantadine, fluorescent dye [5(6)-carboxyfluorescein], and Arg-Gly-Asp (RGD) peptide-targeting ligands assisted by an adamantine linker. The loading ratio of 5(6)-carboxyfluorescein is as high as 110% with a drug concentration of 0.45 mg mL(-1). The cyclic RGD-functionalized nanohybrid exhibits remarkable targeting for HeLa cells.

Ultra-sensitive complex as phosphorescence probe for the determination of trace protein

β-CD-HMTA-L-Tyr complex, formed in the host guest inclusion reaction carried out between host molecule β-cyclodextrin (β-CD) in β-CD-HMTA (HMTA is methenamine) and guest molecule L-tryptophan (L-Tyr), possessing the characteristic of room temperature phosphorescence (RTP). Bovine serum albumin (BSA) reacted with L-Tyr to form a complex of cage structure bringing in the sharply RTP signal quenching of L-Tyr. Based on the above facts, a new ultra-sensitive solid substrate room temperature phosphorimetry (SSRTP) for the determination of trace protein has been established using β-CD-HMTA-L-Tyr complex as a phosphorescence probe. Under the optimum conditions, the linear range of this method was 0.0040–0.56agspot−1 with a detection limit (D.L.) as 0.92zgspot−1, and the regression equations of working curve was ΔIp=0.8239+162.5 mBSA (agspot−1, n=8) with the correlation coefficient (r) of 0.9994. The relatively standard deviation (RSD) and the recovery of SSRTP were 4.8–3.3% and 96.7–102%, respectively, indicating that this method had good repeatability. The proposed phosphorescence probe has been applied in the detection of protein in real samples and the results agreed well with those obtained with SSRTP using methylene blue-sodium tetraphenylborate as phosphorescence probe. Meanwhile, the reaction mechanism for the determination of trace protein with β-CD-HMTA-L-Tyr complex as phosphorescence probe has been discussed.

New Approach for the Determination of Tricyclic Antidepressant Amitriptyline Using <i>β</i>-Cyclodextrin-PEG System via Spectrophotomerty

A new and simple procedure for the spectrophotometric determination of the tricyclic antidepressant drug amitriptyline is proposed. The method is based on enhancement of sensitivity of the [AMIYTP]+ β-cyclodextrin and PEG molecules involved in formation of molecules inclusion complex, in presence of polyethylene glycol (PEG) medium. The mole ratio of [AMIYTP]+ β-cyclodextrin and PEG molecules in inclusion complex were determined by the curve fitting method. The value of molar absorptivity of {[AMIYTP: (β CD)] PEG} complex in term of the drug lies in rage of (2.20 - 2.23) × 104 L·mole–1·cm–1 at absorption maximum 242 nm. The slope, intercept and correlation co-efficient were found to be 14.21, 0.0046, and 0.998, respectively. The effect of analytical variables on the determination of the drug and composition of the ion associated complex are discussed in the paper. This method is applicable in the determina-tion of amitriptyline in the pharmaceutical preparations.

Enhanced production of volatile fatty acids (VFAs) from sewage sludge by β-cyclodextrin

Organic matter in sewage sludge can be converted into volatile fatty acids (VFAs) as renewable carbon sources. This work for the first time demonstrates that β-cyclodextrin (β-CD) molecules enhance sludge hydrolysis for production of VFAs. With 0.2gβ-CDg−1 dried solids (DSs), the increment rate for VFAs peaked at 4200gg−1DSsg−1 β-CD, with acetate and propionate as the predominant VFAs. Compositional and microbial community analyses confirm that the β-CD molecules break a cell’s membrane, such that it releases intracellular substances. Although β-CD molecules inhibited activities of methanogens, they did not impair those of acid-forming bacteria, thereby demonstrating that β-CD-assisted VFAs are renewable organic carbon sources, except in anaerobic digestion processes.

Mesoporous silica particles for selective detection of dopamine with β-cyclodextrin as the selective barricade

A mesoporous silica nanoparticle (MSN) based fluorescent sensor for dopamine was constructed with probes inside particle pores and β-cyclodextrin (β-CD) molecules on the particle surface as the selective barricade. The synergistic action of both the hydrophilic rim and hydrophobic cavity of β-CD ensures that the sensor can distinguish dopamine from other biological competitors.