Β-cyclodextrin Inclusion Complex Research Articles

Inclusion Complex of 2-Methyl Mercapto Phenothiazine with Hydroxy Propyl β-Cyclodextrin: Characterization and Cytotoxic Activity Evaluation

Abstract A host-guest inclusion complex of hydroxy propyl β-cyclodextrin (HBCD) and 2-methyl mercapto phenothiazine (2MMPT) was prepared and investigated in liquid state and in solid state. In liquid state, UV-visible and fluorescence spectroscopic methods are used to investigate the inclusion complex. The binding constant of 2MMPT: HBCD inclusion complex was calculated using Benesi-Hildebrand plot. The 1:1 stoichiometric ratio of inclusion complex was derived from Benesi-Hildebrand plot and Job’s plot of continuous variation method. The solid HBCD: 2MMPT inclusion complex was prepared by coprecipitation method and characterized using FT-IR, 1 H NMR, 13 C NMR, and ESI-MS analytical methods. The cytotoxicity of HBCD: 2MMPT inclusion complex was studied on human breast cancer cell line MCF 7 showed that the cell cytotoxicity of HBCD: 2MMPT inclusion complex was close to free 2MMPT and inclusion complexation with HBCD retained the anticancer activity of 2MMPT.

Functional self-assembled nanovesicles based on β-cyclodextrin, liposomes and adamantyl guanidines as potential nonviral gene delivery vectors.

Multicomponent self-assembled supramolecular nanovesicles based on an amphiphilic derivative of β-cyclodextrin and phosphatidylcholine liposomes (PC-liposomes) functionalized with four structurally different adamantyl guanidines were prepared and characterized. Incorporation efficiency of the examined adamantyl guanidines as well as size and surface charge of the prepared supramolecular nanovesicles was determined. Changes in the surface charge of the prepared nanovesicles confirmed that guanidinium groups were exposed on the surface. ITC and 1H NMR spectroscopy complemented by molecular dynamics (MD) simulations were used to elucidate the structural data and stability of the inclusion complexes of β-cyclodextrin and adamantyl guanidines (AG1-5). The results are consistent and point to a significant contribution of the guanylhydrazone residue to the complexation process for AG1 and AG2 with β-cyclodextrin. In order to evaluate the potential of the self-assembled supramolecular nanomaterial as a nonviral gene delivery vector, fluorescence correlation spectroscopy was used. It showed that the prepared nanovesicles functionalized with adamantyl guanidines AG1-4 effectively recognize and bind the fluorescently labelled DNA. Furthermore, gel electrophoretic assay confirmed the formation of nanoplexes of functionalized nanovesicles and plasmid DNA. These findings together suggest that the designed supramolecular nanovesicles could be successfully applied as nonviral gene delivery vectors.

Drugs–β-Cyclodextrin inclusion complex: Would be a new strategy to improve Antihypertensive Therapy?

Drugs–β-Cyclodextrin inclusion complex: Would be a new strategy to improve Antihypertensive Therapy?

Characterization, formulation and evaluation of glibenclamide with β-cyclodextrin inclusion complexes tablets

Background: Glibenclamide is an oral antidiabetic drug which is practically insoluble in water. Formation of s-cyclodextrin inclusion complex was able to increase glibenclamide solubility. Objective: Aims of this study are to characterize, formulate and evaluate inclusion complex tablets of glibenclamide to meet the requirements in Pharmacopeia. Methods: Inclusion complex was prepared in a 1: 1 and 1: 2 molar ratio by spray drying method. Characterization were performed by using Fourier Transform Infrared (FTIR) spectroscopy and Scanning Electron Microscope (SEM). Further, it was formulated into tablets by direct compression technique using primojel and crospovidone as disintegrants. Uniformity weight, hardness, friability, disintegration, and tablets were evaluated include dissolution. Dissolution studies of inclusion complex were performed by using United States Pharmacopeia (USP) II apparatus. Drug concentration dissolution was determined with high pressure liquid chromatography (HPLC). Results: Result of FTIR and SEM provided evidence of glibenclamide and s-cyclodextrin complex formation after using spray drying methods. The tablet evaluation with primojel and crospovidone as disintegrant showed that increase concentration of disintegrant would increase disintegration time of the tablets. All of the formulas meet the requirements in the Pharmacopoeia. Conclusion: The inclusion complex of glibenclamide–s cyclodextrin successfully used for enhancing the solubility of glibenclamide. The tablets meet the requirements in Pharmacopeia.

Development of active packaging film containing bioactive components encapsulated in [formula omitted]-cyclodextrin and its application

Incorporating natural antimicrobials, such as Citral (CI) and trans-cinnamaldehyde (TC), into packaging film using a melt extrusion method is not possible because of thermal sensitivity of the compounds. Encapsulating these antimicrobials in an inclusion complex such as β-Cyclodextrin, however, can preserve their bioactive effectiveness beyond the film extrusion stage, and, in addition, possibly control their release rate afterward. This study investigated properties of an active packaging film containing bioactive components encapsulated in β-Cyclodextrin. Specifically, physical and mechanical properties of film were measured, the release rate of CI and TC from film were determined, thermal stability of β-Cyclodextrin inclusion complex of citral (β-CD-CI) and trans-cinnamaldehyde (β-CD-TC) were evaluated, and the preservative function of films enhanced with the antimicrobial complexes were verified in packaged chilled beef. The results demonstrated EVOH film containing β-cyclodextrin inclusion complex had a low diffusion coefficient and high equilibrium concentration of natural antimicrobials (CI and TC) in food simulants, and extended shelf life of beef about 4 days at 4 ± 1 °C. In general, active compounds encapsulated into β-Cyclodextrin as an inclusion complex had high thermal stability and slow release rate, which resulted in prolonging shelf life of chilled beef.

Associations of Water-Soluble Macrocyclic Hosts with 4-Aminoazobenzene: Impact of pH.

An investigation of the pH effect on the inclusion complexes of β-cyclodextrins and calixarenesulfonates with 4-aminoazobenzene was conducted both by experiments and molecular simulations. The whole thermodynamic characterizations of the association between hosts and 4-aminoazobenzene ( K, Δr G0, Δr H0, and TΔr S0) were determined by UV-visible spectroscopy. β-Cyclodextrin inclusion complexes are not affected by pH change unlike those obtained with calixarenes. All the studied systems were enthalpically favored. Nevertheless, the entropic behavior is different depending on the host. In order to interpret these experimental results, molecular simulations were used to calculate the number of atoms inserted into the cage-like host compounds and the number of water molecules expelled from the cavity.

Exploring Existence of Host-Guest Inclusion Complex of β-Cyclodextrin of a Biologically Active Compound with the Manifestation of Diverse Interactions

The host–guest interaction of p-nitro benzaldehyde as guest β-Cyclodextrins have been investigated which have significant applications in the field of medicine such as controlled drug delivery. The 1H NMR study confirms the formation of inclusion complex while surface tension and conductivity studies support the formation inclusion complex with 1:1 stoichiometry. The stoichiometry of the inclusion complex was also supported with Job’s plot method by UV-Visible spectroscopy. FT-IR spectra and SEM study also support the inclusion process. Association constants of the inclusion complexes have been calculated using the Benesi–Hildebrand method, while the thermodynamic parameters have been estimated with the help of van’t Hoff equation.

Preparation and Characterization of Butachlor/(2-Hydroxypropyl)-β-cyclodextrin Inclusion Complex: Improve Soil Mobility and Herbicidal Activity and Decrease Fish Toxicity.

A water-soluble inclusion complex for butachlor was prepared by complexation with (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD). Phase solubility results indicated a 1:1 stoichiometric ratio with an apparent stability constant of 864.3 M-1 in the obtained solid complex. The formation of the complex was confirmed by 1H nuclear magnetic resonance, Fourier transform infrared, and differential scanning calorimetry spectra. Coupled with the molecular docking results, butachlor was considered to be completely included in HP-β-CD cavity. Butachlor complexation with HP-β-CD decreased its adsorption capacity and enhanced its mobility in soil. The inclusion complex displayed better herbicidal activities than free butachlor. The 96 h median lethal concentration values of the inclusion complex and free butachlor was 2.30 and 0.65 mg L-1, respectively, for zebrafish, indicating that the complexation could significantly reduce toxicity to fishes. The present study provides an approach to develop environment-friendly formulations using CDs for herbicides.

The inclusion complex of carvacrol and β-cyclodextrin reduces acute skeletal muscle inflammation and nociception in rats.

Skeletal muscle inflammation is strongly associated with pain and may impair regeneration and functional recovery after injury. Since anti-inflammatory and antinociceptive effects have been described for the inclusion complex of carvacrol and β-cyclodextrin (βCD-carvacrol), this study investigated the effects of βCD-carvacrol in a model of acute skeletal muscle inflammation. Muscle injury was induced in male Wistar rats by injection of 3% carrageenan in the gastrocnemius muscle. Rats were orally pretreated with saline (vehicle) or βCD-carvacrol (20, 40, 80 and 180 mg/kg) one hour before administration of carrageenan. The injection of carrageenan in the gastrocnemius muscle increased tissue myeloperoxidase (MPO) activity (p < 0.001), edema (p < 0.001) and the levels of tumoral necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, macrophage inflammatory protein (MIP-2), but not IL-10 levels. Also, it increased mechanical hyperalgesia and decreased the grip force of animals. Pretreatment with βCD-carvacrol (80 or 160 mg/kg) significantly decreased muscle MPO activity and edema 24 h after injury in comparison to vehicle-pretreated group. Animals pretreated with βCD-carvacrol (160 mg/kg) presented significantly lower levels of IL-1β, IL-6 and MIP-2 and higher levels of IL-10 six hours after induction and lower levels of TNF-α and MIP-2 after 24 h when compared to the vehicle group. Pretreatment with βCD-carvacrol also reduced mechanical hyperalgesia and limited the decrease of grip force (80 or 160 mg/kg; p < 0.001) 6 and 24 h after injury. These results show that βCD-carvacrol reduces inflammation and nociception in a model of acute injury to skeletal muscles.

On improving the spectral response of organic dyes sensitizer based on β-cyclodextrin inclusion complex

The effect of inclusion complex on the spectral response, molar extinction coefficient and the conduction mechanism of some organic dyes were studied. β- cyclodextrin inclusion complex strategy was examined on 3 different azo dyes, 2-(10-Hydroxy-anthracen-9-ylazo)-benzoic acid, 10-((4-hydroxyphenyl)diazenyl)anthracene-9-ol and N-(4,6-dimethylpyrimidin-2-yl)-4-(8-hydroxyquinolin-5-yl)diazenyl)benzenesulfonamide. The chemical structure of the obtained dyes was characterized by FTIR, 1H NMR and mass spectral studies. Inclusion complex strategy leads to get organic dyes with broader spectral response and higher molar extinction coefficient.

Pharmaceutical applications of spouted beds: A review on solid dosage forms

Spouted beds (SBs) have a long history of successful applications for preparation of solid dosage forms of pharmaceuticals. The well-known versatility of SBs, provided by different design and operational factors, and their efficient mixing of solids allow for engineering of technological characteristics of pharmaceutical solid forms. Particle properties like morphology, size, porosity, flowability, and dissolution rate can be improved by managing geometric and operational conditions for spouting. Drying is probably the most disseminated operation for pharmaceutical processing in SBs, and many studies have investigated drying of medicinal plant extracts such as achiote (Bixa orellana sp.), guarana (Paullinia cupana sp.), passion flower (Passiflora alata D.), and rosemary (Rosmarinus officinalis L.) with excellent pharmacotechnical and stability results. Another important application is coating of tablets and gelatin capsules, and previous studies have shown that SBs and spout–fluid beds may be advantageous over traditional pan coating, especially for polymeric film coating. Recently, an alternative process for improving drug bioavailability has involved preparation of β-cyclodextrin inclusion complexes in SBs. The first study to propose SBs for this pharmaceutical application explored the advantage of obtaining solid forms of inclusion complexes in just one step, and obtained expressive increases in drug solubility. The technique has been applied in subsequent studies on inclusion complexes of the medication carvedilol and uxi (Endopleura uchi L.) extracts.

Binding, and thermodynamics of β-cyclodextrin inclusion complexes with some coumarin laser dyes and coumarin-based enzyme substrates: a simulation study

This paper addresses modelling the nature of interactions between β-CD and some coumarins including recently reported novel sulphur analogues to form inclusion complexes of appealing medicinal, photochemical and photophysical properties. The binding energy and the total stabilization energy (EONIOM) are used to confirm the most favorable inclusion complex structure. Thermodynamic parameters reveal exothermic inclusion reaction in gas phase. Thermal stability of fluorescent enzyme substrate of coumarin nucleus increases in the order: gas < cyclohexane < water, indicating better stability in water. Furthermore, molecular characteristics such as optimized geometries, MO’s and electrostatic potential energy map surfaces and energies are reported and correlated with some reactivity indices. Our results validated the experimentally available data reported in the literature. Inclusion complexes of β-CD with coumarins should result in improving its laser efficiency in environmentally benign aqueous medium.

Inclusion complexes of cysteinyl β-cyclodextrin with baicalein restore collagen synthesis in fibroblast cells following ultraviolet exposure.

Baicalein, a bioactive flavonoid, has poor water solubility, thereby limiting its use in a wide range of biological applications. In the present study, we used inclusion complexes of cysteinyl β-cyclodextrin (β-CD) with baicalein to enhance the stability and solubility of baicalein in aqueous solution. We examined the effects of inclusion complexes of cysteinyl β-CD on collagen synthesis following ultraviolet (UV) irradiation, as well as the mechanisms underlying its effects. Our findings demonstrated that baicalein significantly restored collagen synthesis in the UV-exposed human fibroblast Hs68 cells. In addition, synthetic cysteine functionalized β-CDs were found to promote baicalein-induced collagen synthesis. Inclusion complexes of cysteinyl β-CDs with baicalein significantly upregulated the protein expression of type I collagen and activated the transcription of type I, II, and III collagen. Inclusion complexes of cysteinyl β-CDs with baicalein also downregulated matrix metalloproteinase -1 and -3, and α-smooth muscle actin expression. In addition, inclusion complexes of cysteinyl β-CDs with baicalein attenuated the expression of caveolin-1, but this treatment enhanced the UV-induced phosphorylation of Smad in the transforming growth factor-β pathway. These results suggested that the newly synthesized derivative of CD can be used as a complexing agent to enhance the bioavailability of flavonoids such as baicalein, especially in restoring collagen synthesis.

Liquid crystals-based sensor for the detection of lithocholic acid coupled with competitive host-guest inclusion.

A simple, low-cost and label-free strategy for detecting lithocholic acid (LCA) was designed at the liquid crystals (LCs)/aqueous interface via competitive host-guest inclusion. In this method, sodium dodecyl sulfate (SDS) was initially adsorbed on the fluid interface and induced LCs to adopt the homeotropic ordering. Inclusion complexation of SDS and β-cyclodextrin (β-CD) disturbed interaction between LCs and SDS and evoked LCs to keep a tilted alignment. When injecting LCA into the mixed solution of SDS and β-CD, SDS excluded from the cavity of β-CD by competitive host-guest inclusion and could be re-adsorbed at the LCs/aqueous interface, resulting in the orientational transition of LCs from tilted to homeotropic state. Correspondingly, a bright-to-dark optical response was observed under polarized optical microscope (POM). The as-prepared LCs-based sensor could detect LCA as low as about 2 μM in aqueous solution. Moreover, the practicability of the approach was validated by monitoring the known amount of LCA in human urine. This work offers an appealing approach for the detection of LCA which has a great potentiality in clinical diagnosis.

Rice spouted bed for manufacturing inclusion complexes of Endopleura uchi L extracts in β-cyclodextrin

Uxi (Endopleura uchi) is a plant from the Brazilian Amazon. It has many biological activities that are attributed to its main active component, bergenin (BG), which has low water solubility. The aim of this work was to obtain β-cyclodextrin (β-CD) inclusion complexes of uxi using lyophilized cooked rice as the solid substrate. The process was studied using a Box–Behnken design with the solution feed rate, molar ratio of β-CD to BG, and rice bed load as factors. These factors greatly affected the product bulk density, angle of repose, water content, and BG content, loss, and water solubility. The optimum process conditions determined using a desirability functions methodology were an extract feed rate of 1mL/min, a ratio of β-CD to BG of 3:1, and a substrate load of 100g. The predicted values under the optimum conditions were close to the experimental results of a water content of 5.8%±0.2%, BG content of 985.7±15.4μg/g, BG water solubility of 2230.2±21.1μg/mL, and BG loss of 1.2%±0.1%. These results confirm that spouted beds are an important tool for rapid, one-step preparation of pharmaceutical β-CD inclusion complexes in a solid form.

Lidocaine/β-cyclodextrin inclusion complex as drug delivery system

Lidocaine (LC)/β-cyclodextrin (β-CD) inclusion complex was prepared. This complex was confirmed using, UV–vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA) and scanning electron microscope (SEM). This complex was used to prepare hydrogel to be used as topical pain relief. (GII) and compared with gel contains Lidocaine (GI) only. The prepared gel was evaluated by measuring the spreadability, moisture regain, viscosity, pH and drug release profile. The results received showed that the gel properties were improved by introducing the Lidocaine/β-cyclodextrin inclusion complex. The release profiles revealed that, gel with Lidocaine/β-cyclodextrin inclusion complex showed improved sustained release behaviour.

Lippia gracilis essential oil in β-cyclodextrin inclusion complexes: an environmentally safe formulation to control Aedes aegypti larvae.

One of the most efficient ways to prevent arboviruses, such as dengue fever, yellow fever, chikungunya and Zika, is by controlling their vector, the Aedes aegypti. Because this vector is becoming resistant to most larvicides used, the development of new larvicides should be considered. β-Cyclodextrin (β-CD) complexes have been investigated as an interesting way of enabling the use of essential oils in water as larvicides. This study comprised the development of Lippia gracilis essential oil (LGEO) and β-CD inclusion complexes for control of Ae. aegypti. Thermal analysis clearly showed the formation of complexes using kneading and co-evaporation methods. Gas chromatography analysis showed that kneading without co-solvent (KW) gave the highest content (∼15%) of the LGEO major component. Moreover, KW showed that the complex had a 50% lethal concentration (LC50 ; 33 ppm) lower than that of pure LGEO (39 ppm); in other words, complexing LGEO with β-CD improved the larvicidal activity. In addition, LGEO complexed with β-CD (KW) was not harmful to non-target organisms at the concentrations needed to control Ae. aegypti larvae. The inclusion complex with LGEO was a feasible formulation, being economically viable, easy-to-apply and without impact on non-target organisms and, therefore, is a potential alternative larvicide for Ae. aegypti control. © 2018 Society of Chemical Industry.

Interaction of 1-methyl-1-({2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-4-yl}methyl) piperidinium chloride with β-CD: spectroscopic, calorimetric and molecular modeling approaches

Spectroscopic investigation supported by molecular modeling methods has been used to describe the inclusion complex of β-cyclodextrin (β-CD) with 1-Methyl-1-({2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-4-yl}methyl) piperidinium chloride (1MPTMPC) in solution and in solid state. The formation of inclusion complex between the β-CD and the 1MPTMPC has been investigated both in solution and in the solid state. Solution-state complexation between the 1MPTMPC and β-CD was established using 1H NMR spectroscopy and isothermal titration calorimetry (ITC). From the 1H NMR spectroscopic studies, 1:1 complex stoichiometry was deduced with an association constant (K) of 925 M−1. Using an independent binding model, the ITC technique provides a K value of the same order with the one determined by NMR and the thermodynamic parameters ΔH, ΔS and ΔG which reveals driving forces involved during complex formation. The formation of the solid inclusion compound was confirmed by X-ray powder diffraction and differential scanning calorimetry. The most probable conformation of the inclusion complex obtained through a molecular docking investigation corroborates well to ROESY experiment.

Identification of β -cyclodextrin inclusion complex by infrared spectroscopy

Fast and reliable identification of obtaining product is very important in the industrial technology of synthesis of pharmaceutical substances.&#x0D; Objective - to study inclusion complexes of β-cyclodextrin with α-bromizovalerian acid and β-cyclodextrin with mint oil by applying near infrared spectroscopy absorption. Compare the spectra obtained with the spectra of equimolar mechanical mixture of the respective components.&#x0D; Β-cyclodextrin complexes with α-bromizovalerian acid and β-cyclodextrin with mint oil were prepared at a well-known technique. Mechanical mixture of β-cyclodextrin with α-bromizovalerian acid and β-cyclodextrin with mint oil were obtained by mixing the components in a molar ratio of 1:1.&#x0D; This paper shows the possibility using method of absorption near-infrared spectroscopy for rapid identification β-cyclodextrin inclusion complexes, as an example used complexes of β-cyclodextrin with α-bromizovalerian acid and β-cyclodextrin with peppermint oil. By comparing the spectra obtained inclusion complexes with the spectra of equimolar mechanical mixture of the corresponding components proved reliability the identification of the target product and the ability to distinguish between an inclusion complex and the mechanical mixture of the components. It is shown that the near infrared spectra obtained using an instrument Thermo Nicolet IS50, Thermo Scientific, inclusion complexes of β-cyclodextrin with a different guest molecules are different from each other.

Structure–antioxidant activity relationship of β-cyclodextrin inclusion complexes with olive tyrosol, hydroxytyrosol and oleuropein: Deep insights from X-ray analysis, DFT calculation and DPPH assay

Olives and olive oil, a key food type of the Mediterranean diets, are packed with various important polyphenols including oleuropein (OLE), hydroxytyrosol (HTY) and tyrosol (TYR). OLE and HTY are highly powerful antioxidants and play a prime role in the therapeutics of free radical-related diseases. Their molecular stabilities and antioxidant properties can be improved by cyclodextrin (CD) encapsulation. Here, we present a systematic investigation on the inclusion complexes of β-CD–TYR (1), β-CD–HTY (2) and β-CD–OLE (3) by combined single-crystal structure determination, DFT complete-geometry optimization and DPPH antioxidant assay. X-ray analysis and DFT calculation reveal the preference of inclusion geometry with deep protrusion of the aromatic ring moieties of TYR, HTY and OLE from the β-CD O6–H-side, and the common host-guest stabilization scheme via intermolecular O–H⋯O hydrogen bonding interactions. No polyphenol OH group is shielded in the β-CD cavity, in contrast to the structures of β-CD–tea catechins complexes. The established host-guest O–H⋯O hydrogen bonds help to elevate antioxidant capacities of the olive polyphenols upon β-CD encapsulation. The order of antioxidant activity 2 >3 ≫ 1 based on the DPPH measurement is in fair agreement with their relative thermodynamic stabilities derived from DFT calculation.