Beta-cyclodextrin Inclusion Complexes Research Articles

Curcumin-sulfobutyl-ether beta cyclodextrin inclusion complex: preparation, spectral characterization, molecular modeling, and antimicrobial activity

Urinary tract infections (UTIs) caused by Gram-negative bacteria E. coli is responsible for 80–90% of uncomplicated cases in women. The increased prevalence of antibiotic resistance has made the management of UTIs more challenging. Plant-derived compounds have long been used to treat various diseases, and constitute an alternative to antibiotic resistance. Curcumin (CUR), a naturally occurring polyphenolic phytoconstituent obtained from Curcuma longa is endowed with diverse medicinal properties. The present study aims to form a complex of CUR with Sulfobutyl ether-β-cyclodextrin (SBEβCD) to overcome the poor solubility and bioavailability of CUR and to evaluate the antimicrobial activity of CUR-SBEβCD. Phase solubility studies and spectral characterization showed the entrapment of CUR in the SBEβCD cavity. In silico docking studies performed to investigate the complexation process of CUR with SBEβCD, revealed that the methoxy group and OH group of CUR interacted with SBEβCD. The cytotoxicity and HET-CAM assays confirmed that CUR-SBEβCD was non-irritant. The prepared complex investigated with the disc diffusion method showed antimicrobial activity with a zone of inhibition (ZOI) of 13 mm against Escherichia coli (E. coli) and 11.5 mm against Staphylococcus aureus (S. aureus) whereas CUR alone did not show any ZOI. It can be concluded that prepared CUR-SBEβCD demonstrated superior antimicrobial activity and therefore can be a promising alternative for the treatment of UTIs. Communicated by Ramaswamy H. Sarma

Encapsulation of volatile oils with antimicrobial activity in chitosan-βCD molecular inclusion complexes by spray drying

Binary and ternary molecular inclusion complexes (MICs) of beta-cyclodextrin (βCD - binary), and chitosan-βCD (ternary) loaded with Lippia sidoides (LS) and Syzygium aromaticum (SA) volatile oils (VOs—pure and in 1:1 mixtures) were engineered by a modified slurry method followed by spray drying. Eugenol and Thymol, the major constituents of SA and LS VOs, were successfully retained in MICs, showing good values of the encapsulation efficiency (EE), molar ratio (MR), and VOs load (DL). EEs were higher for the pure VOs (68.7 ± 1.6 to 86.1 ± 4.0% w/w) compared to their mixtures (37.8 ± 1.4 to 65.9 ± 2.4% w/w). The chitosan addition increased the Thymol’s EE, while for Eugenol, an opposite effect was exhibited. The MICs formed showed slight changes in the volatiles' composition, evidencing a selective encapsulation of the VOs constituents. The effects of processing conditions on moisture content, water activity, and particle size were negligible. The reported results suggest the feasibility of the complexation protocols proposed to manufacture novel binary and ternary complexes of βCD and chitosan.

Preparation and Characterization of Disulfiram and Beta Cyclodextrin Inclusion Complexes for Potential Application in the Treatment of SARS-CoV-2 via Nebulization.

Disulfiram (DS), known as an anti-alcoholism drug, has shown a potent antiviral activity. Still, the potential clinical application of DS is limited by its low water solubility and rapid metabolism. Cyclodextrins (CDs) have been widely used to improve the solubility of drugs in water. In this study, five concentrations of hydroxypropyl β-cyclodextrin (HP) and sulfobutyl ether β-cyclodextrin (SBE) were used to form inclusion complexes of DS for enhanced solubility. Solutions were freeze-dried, and the interaction between DS and CD was characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). In addition, the nebulization properties of the DS–CD solutions were studied. The aqueous solubility of DS increased significantly when loaded to either of both CDs. The phase solubility of both complexes was a linear function of the CD concentration (AL type). Furthermore, physicochemical characterization studies showed a potent inclusion of the drug in the CD–DS complexes. Aerosolization studies demonstrated that these formulations are suitable for inhalation. Overall, the CD inclusion complexes have great potential for the enhancement of DS solubility. However, further studies are needed to assess the efficacy of DS–CD inclusion complexes against SARS-CoV-2 via nebulization.

Michler's Ketone: β-Cyclodextrin Host-Guest Inclusion Complex for Enhancing the Ultraviolet Protection Factor of Poplin Cotton Fabric.

Michler's ketone (4,4' bis(N,N-dimethylamino)benzophenone) mk is a potential ultraviolet radiation (UVR) absorber in various materials. In this study, we have tested the UVR filtering ability of mk on cotton fabric. The beta-cyclodextrin (β-CD) inclusion complex of mk enhances ultraviolet protection factor (UPF) drastically. The impact of β-CD on the UVR filtering of mk are demonstrated by investigating the guest (mk:absorbers)-host (β-CD:enhancer) inclusion complex. Spectral and molecular docking analysis of mk:β-CD complex infers the vertical insertion of the guest molecule by positioning -C=O group of mk at the center of the host molecule with the exclusion of the terminal atoms of guest molecule outside the β-CD cavity. Thus, the host; β-CD renders an inflexible fit to the guest:mk. The inflexible fit of mk into the β-CD cavity enhances the UVR dissipation when it is incorporated on the poplin cotton fabric. With UPF = 46 mk:β-CD complex is proposed as a potential UVR absorber suitable for manufacturing sun protective textiles. The holding of mk by β-CD enhances the UVR dissipation and hence facilitates the native red-shifted emission and non-radiative relaxation by the formation of twisted intramolecular charge transfer in mk.

Solubility and Dissolution Enhancement of Dexibuprofen with Hydroxypropylbetacyclodextrin (HPβCD) and Poloxamers (188/407) Inclusion Complexes: Preparation and In Vitro Characterization.

The objective of this study was to improve the dissolution and solubility of dexibuprofen (DEX) using hydroxypropyl beta cyclodextrin (HPβCD) inclusion complexes and also to evaluate the effect of presence of hydrophilic polymers on solubilization efficiency of HPβCD. Three different methods (physical trituration, kneading and solvent evaporation) were used to prepare binary inclusion complexes at various drug-to-cyclodextrin weight ratios. An increase in solubility and drug release was observed with the kneading (KN) method at a DEX/HPβCD (1:4) weight ratio. The addition of hydrophilic polymers poloxamer-188 (PXM-188) and poloxamer-407 (PXM-407) at 2.5, 5.0, 10.0 and 20% w/w enhanced the complexation efficiency and solubility of DEX/HPβCD significantly. Fourier-transform infrared (FTIR) analysis revealed that DEX was successfully incorporated into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) revealed less crystallinity of the drug and its entrapment in the cyclodextrin molecular cage. The addition of PXM-188 or PXM-407 reduced the strength of the DEX endothermic peak. With the addition of hydrophilic polymers, sharp and intense peaks of DEX disappeared. Finally, it was concluded that PXM-188 at a weight ratio of 10.0% w/w was the best candidate for improving solubility, stability and release rate of DEX.

Polymorphism and β-cyclodextrin complexation of methyldrostanolone

2α,17α-dimethyl-4,5α-dihydrotestosterone known as methyldrostanolone is a synthetic anabolic-androgenic agent which belongs to the steroid group. The crystal structures of two methyldrostanolone polymorphs were determined by single crystal X-ray diffraction. Intermolecular interactions, crystal lattice energies and structural features of the two polymorphs were investigated, and steroid rings were analyzed in terms of conformational analysis. The formation of beta-cyclodextrin inclusion complex was investigated by X-ray powder diffraction, Fourier-Transform infrared spectroscopy and DTA/TGA thermal analysis.

An environmentally safe formulation with enhanced solubility and fungicidal activity: Self-assembly and characterization of Difenoconazole-β-CD inclusion complex

Since pesticides have the disadvantages of low utilization rate and pollution to the surrounding environment, it is necessary to consider the development of new pesticide formulations. Difenoconazole (DZ), a common fungicide with poor water solubility, needs to be mixed with a large number of additives during use, which results in excessive use of organic solvents and pesticide residues. In this study, inclusion complex of beta-cyclodextrin (β-CD) and DZ was synthesized by ultrasonic method and was then aim to enhance the water solubility and its antifungal activity against Gibberella sp. of DZ. X-ray diffraction (XRD), nuclear magnetic resonance (1H NMR) analysis and molecular modeling techniques were applied to characterized the formation of DZ/β-CD inclusion complex, the DZ:β-CD stoichiometric ratio of the prepared inclusion complex was calculated in accordance with the result of 1H NMR. Increased water solubility of inclusion complex was illustrated by phase solubility studies. The inclusion complex showed a more significant fungicidal effect against Gibberella sp. than original DZ in the fungicidal effect assay. The inclusion complexation of β-CD on DZ was a new pesticide formulation and provided new development ideas for the application of DZ in agriculture.

Preparation and Characterization of Flurbiprofen/β-Cyclodextrin Inclusion Complex

This study aims to ameliorate the water solubility of flurbiprofen by using β-cyclodextrin (β-CD). The drug/ligand 1:1 (M/M) stoichiometry was determined based on the effect of β-CD on the solubility of flurbiprofen. Several methods of preparing flurbiprofen/β-CD inclusion complex were investigated and a solvent method using hot water to dissolve the starting materials was selected. The selected method showed a lot of advantages such as high complexing ability, good product yield, simple and eco-friendly process. The obtained product was characterized using various analytical techniques such as high-performance liquid chromatography, differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscopy. The product had a predominantly amorphous form with clathrate particles of about 2-7 µm in size, irregular edges and rough surfaces. The study results show that in the complexing process, flurbiprofen replaced water molecules located in the conical cavity of β-CD. The complex contained 19.91% flurbiprofen by mass with water solubility at 37°C was 1,100 µg/ml. The results also show that the complexing with β-CD significantly improved the water solubility of flurbiprofen by both speed and level.
 Keywords
 Flurbiprofen, β-cyclodextrin, inclusion complex, water solubility, preparation, characterization.
 References
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Comparative studies of directly loaded and cyclodextrin-mediated release of Theophylline and evaluation of biodegradation studies of HPNs

Theophylline, also known as 1,3-dimethylxanthine, is a bronchodilator used to cure respiratory problems. With a view to improve drug solubility, therapeutic index, stability and controlled drug delivery of Theophylline, the Host–Guest, solid inclusion compounds of Theophylline and beta-cyclodextrin were prepared through traditional methods and microwave-prompted technique. All the characterization techniques like FESEM, FTIR, PXRD 1HNMR and DSC confirmed the MW irradiation method is the best method to form true inclusion complexes of beta-cyclodextrin and drug Theophylline. The drug release of directly loaded TP was compared with inclusion loaded hybrid polymer networks (HPNs) of chitosan and gelatin synthesized in air conditions. It was found that TP was released in a controlled manner as compare to the HPNs loaded with TP directly. Secondly, the drug release through the differently prepared ICs was also compared and found that the microwave-triggered synthesis of ICs is a brilliant method for the sustained release of the TP. It is a competent, green, quick and environment friendly in comparison to the traditional methods. In drug release kinetics, the values of n were found as 1.143, 0.501 and 0.797 at pH of 2, 7 and 7.4, respectively, which confirmed the non-Fickian diffusion at pH of 7 and 7.4, but at acidic pH conditions, the value of diffusion exponent was found to be greater than one, and it is the non-Fickian super case II diffusion. The continuous development of biodegradation at diverse steps was inspected by weight loss and with different characterization techniques like FTIR and FESEM, which revealed the hydrogel networks prepared in air conditions are biodegradable and the composting process of biodegradation was established as a more efficient method than soil burial approach.

Ionic liquid@β-cyclodextrin-gelatin composite membrane for effective separation of tea polyphenols from green tea

A new kind of multi-component membrane was prepared by combining gelatin solution, porogen and an inclusion complex of ionic liquid (IL) and beta-cyclodextrin (β-CD) in a simple physical manner for selective separation of tea polyphenols (TPs) from green tea crude extracts. After screening, it was found that the resulting membrane containing the IL of dicationic N-vinylimidazole proline salt ([VIm]2C3[l-pro]2) had the excellent performance for the enrichment of the target molecules. Then the newly-developed film was comprehensively characterized by scanning electron microscopy, conductivity, thermogravimetry and spectral analysis. Under pressure driving, the adsorption from an aqueous solution of a mixture of TPs and theophylline on IL@β-CD-Gel membrane showed that the adsorption capacity for TPs was 303.45 mg/g with removal percentages of 94.38%. The experimental data fit well with pseudo-second-order model and Freundlich model. By using this composite material, a new technology of membrane separation for selective adsorption of TPs was finally established.

Chitosan-N-acetylcysteine modified HP-β-CD inclusion complex as a potential ocular delivery system for anti-cataract drug: Quercetin

The aim of this study was to develop a novel ocular drug delivery system based on the hydroxypropyl beta cyclodextrin (HP-β-CD) inclusion complex coated with the synthesized chitosan-N-acetyl-l-cysteine conjugate (CS-NAC) for the hydrophobic drug quercetin. The inclusion complex was prepared by the solvent evaporation method, and the concentration of HP-β-CD and CS-NAC was optimized by isolated corneal penetration test. The optimized concentration of HP-β-CD and CS-NAC was 20% (w/v) and 0.1% (w/v), respectively. The CS-NAC/quercetin-HP-β-CD had the effect on improving the ocular penetration with little ocular irritation and could increase the ocular distribution significantly. Meanwhile, Coumarin-6 (C6) labelled CS-NAC/C6-HP-β-CD possessed enhanced fluorescence and located deeper into the epithelium of cornea at the same time point compared with the uncoated one. It could also transport drug through the corneal epithelium by intracellular routes except for intercellular routes. Furthermore, it could delay the occurrence of cataract about 1 d when administrated with full-dosage quercetin. The HP-β-CD inclusion complex coated with CS-NAC is a safe and promising ocular drug delivery system for improving the bioavailability and corneal penetration of hydrophobic drug like quercetin.

Utility of Sulfobutyl Ether beta-Cyclodextrin Inclusion Complexes in Drug Delivery: A Review

The potential of beta-cyclodextrins as a pharmaceutical aid has been established through several decades of research. However, some beta-cyclodextrins are reported to be toxic causing deleterious effects on long term usage. In the recent past, sulfobutyl ether beta-cyclodextrin, a modified beta-cyclodextrin has captured interest as a comparatively safer and effective beta-cyclodextrin for increasing the solubility and the bioavailability of biopharmaceutical classification system class II drugs. Sulfobutyl ether beta-cyclodextrin has demonstrated immense potential in addressing solubility and stability issues associated with formulation of drugs. Till date no comprehensive report on their utility in drug development has been published. Hence, this review focusses on the structure, properties, preparation techniques and applications of sulfobutyl ether beta-cyclodextrin inclusion complexes. Investigation of the feasibility of forming stable inclusion complexes of sulfobutyl ether beta-cyclodextrin and various drugs as guest molecules using molecular modelling techniques have been elaborated in the review. Incorporation of sulfobutyl ether beta-cyclodextrin complexes into novel drug delivery systems (liposomes and nanoformulations) have been summarized along with various methods of preparation and the clinical safety. Molecular modelling approach discussed in this review, coupled with wet-lab validation of the complexes, will enable a faster transit of the delivery systems into the clinical setting.

Preparation, characterization and molecular modeling studies of the beta-cyclodextrin inclusion complex with benzoguanamine and its analytical application as chemosensor for the selective sensing of Ce4+

The inclusion complex of β-cyclodextrin (β-CD) with benzoguanamine (BGA) has been investigated in three states. UV–Visible and fluorescence spectral techniques are used in liquid state. FTIR, NMR and MASS techniques are used in solid state and virtual state studies are done by molecular simulation work. The binding constants for the formation of 1:1 BGA:β-CD inclusion complex is estimated by UV–Visible and fluorescence spectral techniques. The chemosensory ability of BGA:β-CD complex was investigated thoroughly for various metal cations and we found the emission of complex showed a linear increase in the intensity for Ce4+ with the linearity range of 1000 μM–2000 μM. Sensitivity analysis shows good sensing for Ce4+ with the LOD of 671 μM and LOQ of 2034 μM. Our result suggests that the BGA:β-CD inclusion complex would be promising material for developing solid state sensory device for sensing Ce4+.

Optimisation of β-cyclodextrin inclusion complexes with natural antimicrobial agents: thymol, carvacrol and linalool

Beta-cyclodextrin (β-CD) inclusion complexes with naturally derived antimicrobial (AM) agents: thymol, carvacrol and linalool were prepared using a co-precipitation technique. Conditions including solvent composition, temperature, reaction time and total solvent volume were investigated to optimise the inclusion efficiency (IE) and yield. Electrospray ionisation mass spectrometry was used to confirm the formation of the thymol/β-CD complex and gas chromatography was used to quantify the amount AM agent that was encapsulated, absorbed onto the surface, or remaining in the filtered solvent. The systematic optimisation of the conditions improved both the yield of the complex and the IE of the AM agents compared to previously reported methods that have been applied to other agents. Using a 1:1 mole ratio of the AM agent to β-CD, the optimised parameters resulted in maximum yields of 87, 84 and 86% (w/w) for thymol, carvacrol and linalool, respectively, with IE’s close to 100% (w/w) for each agent.

Encapsulation of clove essential oil in hydroxypropyl beta-cyclodextrin for characterization, controlled release, and antioxidant activity

The aim of this study was to investigate the physicochemical characteristics, release behavior, and antioxidant activity of clove essential oil-hydroxypropyl beta-cyclodextrin (CEO-HPβCD) inclusion complexes. Clove essential oil was encapsulated by the kneading method with hydroxypropyl beta-cyclodextrin in a 1:1 molecular ratio. The entrapment efficiency of the encapsulated particles was 97.04% ± 1.57. The average particle size was 165.87 ± 1.65 nm and polydispersity index was .25 ± .03. In vitro release profile of CEO-HPβCD inclusion complexes indicated slow and sustained release. DPPH scavenging activity of free clove essential oil and encapsulated particles was 25.20% ± 1.02 and 28.70% ± .77, respectively. Total phenolic content of free clove essential oil was 18.59 ± 1.60 mg GAE/100 mg oil while total phenolic content of particles was 22.57 ± 1.48 mg GAE/100 mg oil. The results of the study revealed that using hydroxypropyl beta-cyclodextrin to encapsulate clove essential oil can be beneficial for the food and pharmaceutical industries. Practical applications Clove essential oil has many biological activities due to its major compound eugenol. Choosing the appropriate method is a significant step for keeping active constituents. Encapsulation that is a beneficial process to control of the bioactive components can prevent degradation and loss of active compounds and prolong the shelf life of entrapped materials. This study can lead to use kneading method which is a low cost and easy encapsulation technique, for conservation of volatile active components, so these compounds can be used more intensely in the form of powder.

Cetirizine Dihydrochloride, beta-Cyclodextrin Inclusion Complex by Ethanol Kneading for Taste Masking

Cetirizine dihydrochloride has a very unpleasant bitter taste. To mask the bitter taste, complexation with β-cyclodextrin using ethanol as a kneading solvent was investigated and evaluated by Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, thermogravimetric analysis, simultaneous X-ray diffractometry-differential scanning calorimetry measurement and 1H-nuclear magnetic resonance spectroscopy. Taste was evaluated by human volunteers using an unstructured line scale. The basic characterization of the prepared tablets including in vivo disintegration time and drug dissolution was studied. Fourier transform infrared spectroscopy, differential scanning calorimetry and powder X-ray diffractometry data confirmed the inclusion complex formation. Thermogravimetric analysis, simultaneous X-ray diffractometry-differential scanning calorimetry measurements revealed the reduction of crystalline β-cyclodextrin due to the displacement of water molecules from complex formation. Proton nuclear magnetic resonance spectroscopy indicated an intermolecular interaction between protons of cetirizine dihydrochloride with the cavity of β-cyclodextrin. The prepared complex showed an unstructured line scale with apparent low average rating of 1.70. The inclusion complex-loaded fast disintegrating tablet prepared with direct compression has short disintegration time and good taste with an unstructured line scale with average rating of 0.28. Cetirizine dihydrochloride, β-cyclodextrin inclusion complex was successfully prepared by kneading method using ethanol as solvent. The inclusion complex-loaded fast disintegrating tablet had good taste and good perception in the mouth.

Metadynamics supports molecular dynamics simulation-based binding affinities of eucalyptol and beta-cyclodextrin inclusion complexes

The development of various molecular dynamics methods enables the detailed investigation of association processes, like host–guest complexes, including their dynamics and, additionally, the release of the guest compound.

Alpha- and Beta-Cyclodextrin Inclusion Complexes with 5-Fluorouracil: Characterization and Cytotoxic Activity Evaluation.

Cyclodextrins are natural macrocyclic oligosaccharides able to form inclusion complexes with a wide variety of guests, affecting their physicochemical and pharmaceutical properties. In order to obtain an improvement of the bioavailability and solubility of 5-fluorouracil, a pyrimidine analogue used as chemotherapeutic agent in the treatment of the colon, liver, and stomac cancers, the drug was complexed with alpha- and beta-cyclodextrin. The inclusion complexes were prepared in the solid state by kneading method and characterized by Fourier transform-infrared (FT-IR) spectroscopy and X-ray powder diffractometry. In solution, the 1:1 stoichiometry for all the inclusion complexes was established by the Job plot method and the binding constants were determined at different pHs by UV-VIS titration. Furthermore, the cytotoxic activity of 5-fluorouracil and its complexation products were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on MCF-7 (breast cancer cell line), Hep G2 (hepatocyte carcinoma cell line), Caco-2 (colon adenocarcinoma cell line), and A-549 (alveolar basal epithelial carcinoma cell line). The results showed that both inclusion complexes increased the 5-fluorouracil capability of inhibiting cell growth. In particular, 5-fluorouracil complexed with beta-cyclodextrin had the highest cytotoxic activity on MCF-7; with alpha-cyclodextrin the highest cytotoxic activity was observed on A-549. The IC50 values were equal to 31 and 73 µM at 72 h, respectively. Our results underline the possibility of using these inclusion complexes in pharmaceutical formulations for improving 5-fluorouracil therapeutic efficacy.

Characterization of beta-cyclodextrin inclusion complexes containing an essential oil component

An important issue in food technology is that antimicrobial compounds can be used for various applications, such as the development of antimicrobial active packaging materials. Yet most antimicrobial compounds are volatile and require protection. In the present study, the inclusion complexes of 2-nonanone (2-NN) with β-cyclodextrin (β-CD), were prepared by a co-precipitation method. Entrapment efficiency (EE), thermal analysis (DSC and TGA), X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FT-IR), sorption isotherms and antifungal activity were evaluated for the characterization of the inclusion complex (β-CD:2-NN). A higher EE was obtained (34.8%) for the inclusion complex 1:0.5 than for other molar rates. Both DSC and TGA of the inclusion complexes showed the presence of endothermic peaks between 80°C and 150°C, attributed to a complexation phenomenon. Antimicrobial tests for mycelial growth reduction under atmospheric conditions proved the fungistatic behaviour of the inclusion complexes against Botrytis cinerea.

Characterization of carvacrol beta-cyclodextrin inclusion complexes as delivery systems for antibacterial and antioxidant applications

Carvacrol is a good natural antimicrobial and antioxidant agent; however, its poor aqueous solubility and high volatility limit its application in food systems. Beta-cyclodextrin (ΒCD) is able to encapsulate hydrophobic molecules improving its aqueous solubility and reducing its volatility. ΒCD-carvacrol inclusion complexes were prepared using kneading (KN) and freeze drying (FD) methods. Sizes of ΒCD-carvacrol complexes were 441 ± 12 nm and 899 ± 44 nm and entrapment efficiencies were 83.79 ± 2.89% and 91.31 ± 0.41% for KN and FD BCD-carvacrol complexes, respectively. Polydispersity index was higher (P < 0.05) than 0.1 for both methods, indicating a polydisperse system. Differential thermograms and phase solubility study indicated formation of 1:1 stoichiometry inclusion complex. Trolox Equivalent Antioxidant Capacity (TEAC) values ranged from 7491 to 6421 μmol TE/g among treatments, where KN ΒCD-carvacrol complex showed the lowest (P < 0.05) antioxidant activity. Storage stability of ΒCD-carvacrol complexes proved beneficial to carvacrol encapsulation. Antimicrobial activity against Escherichia coli K12 and Salmonella enterica serovar Typhimurium LT2 showed that all BCD-carvacrol complexes inhibited bacterial growth at lower (P < 0.05) carvacrol concentrations (values ranged from 300 to 350 μg/mL) compared to free carvacrol (≥1000 μg/mL). Results indicate that these ΒCD-carvacrol complexes could have important applications in food systems due to their storage stability and improved antimicrobial activity.