Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration.

Cyclodextrins (CDs) are known for their ability to extract lipid components from synthetic and biological membranes and therefore to induce an increase of membrane permeability. However, the effect of cholesterol (CHOL) content in the membrane on the CD permeabilizing effect was not considered yet. Given that an increase in CHOL content reduces the membrane permeability, the aim of this work was to reveal how CHOL would modulate the CDs effect on the membrane. Hence, liposomes made of dipalmitoyl phosphatidylcholine (DPPC) and various CHOL contents (DPPC/CHOL 100:10, 100:25, 100:50, and 100:100) encapsulating the hydrophilic fluorophore, sulforhodamine B (SRB), were prepared and exposed to the native CDs (α-CD, ß-CD, γ-CD) and four ß-CD derivatives: the randomly methylated-ß-CD (RAMEB), the low methylated-ß-CD (CRYSMEB), the hydroxypropyl-ß-CD (HP-ß-CD) and the sulfobutyl ether-ß-CD (SBE-ß-CD) at different CD/DPPC molar ratios (1:1, 10:1, and 100:1). The membrane permeability was monitored following the release of SRB with time. The results demonstrated that the CDs effect on the membrane depends on the CD type, CD concentration, and membrane CHOL content. The investigated CDs exhibited an instantaneous permeabilizing effect promoting vesicle leakage of SRB from the various membranes; this effect increased with CDs concentration. Among the studied CDs, α-CD, ß-CD, and RAMEB were the most permeabilizing CDs on the different membranes. Similar modifications of SRB release from the various liposomal formulations were obtained with HP-ß-CD, CRYSMEB, and SBE-ß-CD. γ-CD was the less potent CD in affecting the membrane permeability. The CDs effect also depended on the CHOL content: at the CD/DPPC molar ratio (100:1), RAMEB and ß-CD considerably permeabilized the membrane of high CHOL content (50%, 100%) while the remaining CDs showed a decreasing permeabilizing effect upon CHOL content membrane increase.

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies.

A simple method for the preparation of ß-cyclodextrin derivatives containing covalently bonded aldehydes via an imine bond was developed and used to prepare a series of derivatives from 6I-amino-6I-deoxy-ß-cyclodextrin and the following volatile aldehydes - cinnamaldehyde, cyclamen aldehyde, lilial, benzaldehyde, anisaldehyde, vanillin, hexanal, heptanal, citral, and 5-methylfurfural. Subsequently, the rate of release of the volatile compound from selected pro-fragrances, as a function of the environment (solvent, pH), was studied by 1H NMR spectroscopy (for benzaldehyde) and static headspace-gas chromatography (for benzaldehyde, heptanal, and 5-methylfurfural). The aldehyde release rate from the imine was shown to depend substantially on the pH from the solution and the air humidity from the solid state.

Chemical Composition, Antioxidant and Anti-Inflammatory Activities of Clary Sage and Coriander Essential Oils Produced on Polluted and Amended Soils-Phytomanagement Approach.

The potential of essential oils (EO), distilled from two aromatic plants-clary sage (Salvia sclarea L.) and coriander (Coriandrum sativum L.)-in view of applications as natural therapeutic agents was evaluated in vitro. These two were cultivated on a trace element (TE)-polluted soil, as part of a phytomanagement approach, with the addition of a mycorrhizal inoculant, evaluated for its contribution regarding plant establishment, growth, and biomass production. The evaluation of EO as an antioxidant and anti-inflammatory, with considerations regarding the potential influence of the TE-pollution and of the mycorrhizal inoculation on the EO chemical compositions, were the key focuses. Besides, to overcome EO bioavailability and target accession issues, the encapsulation of EO in ß-cyclodextrin (ß-CD) was also assessed. Firstly, clary sage EO was characterized by high proportions of linalyl acetate (51-63%) and linalool (10-17%), coriander seeds EO by a high proportion of linalool (75-83%) and lesser relative amounts of γ-terpinene (6-9%) and α-pinene (3-5%) and coriander aerial parts EO by 2-decenal (38-51%) and linalool (22-39%). EO chemical compositions were unaffected by both soil pollution and mycorrhizal inoculation. Of the three tested EO, the one from aerial parts of coriander displayed the most significant biological effects, especially regarding anti-inflammatory potential. Furthermore, all tested EO exerted promising antioxidant effects (IC50 values ranging from 9 to 38 g L-1). However, EO encapsulation in ß-CD did not show a significant improvement of EO biological properties in these experimental conditions. These findings suggest that marginal lands polluted by TE could be used for the production of EO displaying faithful chemical compositions and valuable biological activities, with a non-food perspective.

Characterization of Cyclodextrin/Volatile Inclusion Complexes: A Review.

Cyclodextrins (CDs) are a family of cyclic oligosaccharides that constitute one of the most widely used molecular hosts in supramolecular chemistry. Encapsulation in the hydrophobic cavity of CDs positively affects the physical and chemical characteristics of the guests upon the formation of inclusion complexes. Such a property is interestingly employed to retain volatile guests and reduce their volatility. Within this scope, the starting crucial point for a suitable and careful characterization of an inclusion complex is to assess the value of the formation constant (Kf), also called stability or binding constant. This task requires the application of the appropriate analytical method and technique. Thus, the aim of the present paper is to give a general overview of the main analytical tools used for the determination of Kf values for CD/volatile inclusion complexes. This review emphasizes on the advantages, inconvenients and limits of each applied method. A special attention is also dedicated to the improvement of the current methods and to the development of new techniques. Further, the applicability of each technique is illustrated by a summary of data obtained from the literature.

The effect of cyclodextrin complexation on the solubility and photostability of nerolidol as pure compound and as main constituent of cabreuva essential oil.

Nerolidol (Ner), a major component of many plant essential oils, is known for its various biological properties. However, the low solubility of Ner in water and its susceptibility to degradation limit its application. The aim of our study was to improve the solubility and photostability of Ner through its encapsulation in different cyclodextrins (CDs). The formation constants of cis-, trans-Ner and their commercial mixture with various CDs (α-CD, ß-CD, γ-CD, HP-ß-CD, RAMEB, CRYSMEB and SBE-ß-CD) were determined by phase solubility studies and confirmed by the spectral displacement UV-visible method. The solubility of cabreuva essential oil (EO) rich in trans-Ner was also evaluated by total organic carbon (TOC) analysis. The encapsulation efficiency (EE %) of Ner in HP-ß-CD solid complexes was assessed by HPLC. The structural characterization of CD/trans-Ner inclusion complex was then conducted by NMR spectroscopy followed by molecular modelling studies. The effect of encapsulation on the Ner photostability was also carried out over time under UVB irradiation. AL-type phase-solubility diagrams were obtained, suggesting the formation of 1:1 CD/Ner inclusion complexes. The solubility of Ner was enhanced by approximately 70-fold in the presence of 10 mM HP-ß-CD. Moreover, high EE % values were obtained for 5:1 and 10:1 HP-ß-CD:Ner molar ratios. NMR and molecular modelling studies revealed the most stable structure for trans-Ner inside the CD cavity with the OH group oriented towards the wider rim of the CD. Finally, CD encapsulation of Ner as pure compound or as main component of the cabreuva EO, protected it from degradation. This effect was more pronounced as the concentration of CD increased. These findings suggested that CDs are promising encapsulating carriers for Ner by enhancing its solubility and stability and thereby its application in food industry.

Ionic liquids and cyclodextrin inclusion complexes: limitation of the affinity capillary electrophoresis technique.

The state of the art of inclusion complex formation between cyclodextrins and ionic liquids is reported. Mechanisms, stoichiometries, and binding constants are summarized and classified by anion. We investigated the supramolecular interactions between the ß-cyclodextrin cavity and six ionic liquids based on 1-dodecyl-3-methylimidazolium by affinity capillary electrophoresis and compared the results with those obtained by isothermal titration calorimetry. We show that the presence of basic or acidic buffers leads to a metathesis reaction, underlining the limitation of the affinity capillary electrophoresis technique.

Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol.

Carvacrol and thymol have been widely studied for their ability to control food spoilage and to extend shelf-life of food products due to their antimicrobial and antioxidant activities. However, they suffer from poor aqueous solubility and pronounced flavoring ability that limit their application in food systems. These drawbacks could be surpassed by encapsulation in cyclodextrins (CDs). Applications of their inclusion complexes with CDs were reported without investigating the inclusion phenomenon in deep. In this study, inclusion complexes were characterized in terms of formation constants (K f), complexation efficiency (CE), CD:guest molar ratio and increase in bulk formulation by using an UV-visible competitive method, phase solubility studies as well as (1)H and DOSY (1)H NMR titration experiments. For the first time, a new algorithmic treatment that combines the chemical shifts and diffusion coefficients variations for all guest protons was applied to calculate K f. The position of the hydroxy group in carvacrol and thymol did not affect the stoichiometry of the inclusion complexes but led to a different binding stability with CDs. 2D ROESY NMR experiments were also performed to prove the encapsulation and illustrate the stable 3D conformation of the inclusion complexes. The structural investigation was accomplished with molecular modeling studies. Finally, the radical scavenging activity of carvacrol and thymol was evaluated by the ABTS radical scavenging assay. An improvement of this activity was observed upon encapsulation. Taken together, these results evidence that the encapsulation in CDs could be valuable for applications of carvacrol and thymol in food.

Effect of cyclodextrin complexation on phenylpropanoids' solubility and antioxidant activity.

The complexation abilities of five cyclodextrins (CDs) with seven phenylpropanoids (PPs) were evaluated by UV-visible spectroscopy, phase solubility studies and molecular modeling. Formation constants (K f), complexation efficiency (CE), PP:CD molar ratio, increase in formulation bulk and complexation energy were assessed. All complexes exhibited a 1:1 stoichiometry but their stability was influenced by the nature and the position of the phenyl ring substituents. A relationship between the intrinsic solubility of guests (S 0) and the solubilizing potential of CD was proposed. Molecular modeling was used to investigate the complementarities between host and guest. Finally, the antioxidant activity of encapsulated PPs was evaluated by scavenging of the stable DPPH radical.

Removal of volatile organic compounds using amphiphilic cyclodextrin-coated polypropylene.

Polypropylene nonwovens were functionalised using a self-assembled, amphiphilic cyclodextrin coating and the potential for water purification by removal of pollutants was studied. As benzene is one of the problematic compounds in the Water Framework Directive, six volatile organic compounds (benzene and five benzene-based substances) were chosen as model compounds. The compounds were tested as a mixture in order to provide a more realistic situation since the wastewater will be a complex mixture containing multiple pollutants. The volatile organic compounds are known to form stable inclusion complexes with cyclodextrins. Six different amphiphilic cyclodextrin derivatives were synthesised in order to elucidate whether or not the uptake abilities of the coating depend on the structure of the derivative. Headspace gas chromatography was used for quantification of the uptake exploiting the volatile nature of benzene and its derivatives. The capacity was shown to increase beyond the expected stoichiometries of guest-host complexes with ratios of up to 16:1.

Investigation of Doehlert matrix conception in novel intrinsically conducting polymers based on selenium nanoparticles for wastewater treatment: Synthesis, characterization, kinetic and chemometric study.

The synthesis of robust intrinsically conducting polymers (ICPs) based on nanoparticles is becoming increasingly attractive to the research community due to the unique properties of these nanocomposites. Indeed, as organic semiconductors, ICPs combine both polymer and metal properties in a single structure. This study presents an innovative approach in which the Doehlert Matrix (DM) is applied to a novel ICP nanocomposite based on polyaniline (Pani) coupled with selenium (Se) loaded mesoporous titania (TiO2) for wastewater treatment by photocatalysis. It includes both the elaboration routes of ICP nanocomposites, characterization of materials by X-ray diffraction (XRD), BET analysis, thermogravimetric analysis (TGA), RAMAN spectroscopy and Fourier transform infrared spectroscopy (FTIR) and photodegradation of methylene blue (MB) as a representative of dye pollutant. In addition, the photocatalytic process has been optimized by a novel DM conception. The effect of the pH of the solution, the catalyst dosage and the initial pollutant concentration was investigated. The optimum conditions were found to be: initial MB concentration of 15 mg/L, the catalyst dosage of 69 mg and pH of 9.6 with an operating time of 75 min, with a coefficient of determination R2 equal to 0.9985. The removal efficiency of BM was close to 97 %. The study shows that the new ICP nanocomposites improve the photocatalytic efficiency compared to pure titania and/or pure Pani. In addition, as the ternary Pani-Se-TiO2 nanocomposite could be obtained from a low-cost synthesis, it is a very promising material for use in wastewater treatment.

Space filling of ß-cyclodextrin and ß-cyclodextrin derivatives by volatile hydrophobic guests.

The inclusion of volatile derivatives of benzene and cyclohexane in ß-cyclodextrin (ß-CD), hydroxypropyl-ß-CD, and hydrophilic ß-CD-thioethers was investigated by static headspace gas chromatography (HS-GC) and molecular modelling. The obtained binding constants strongly increase with the amount of space filling of the CD cavity and the salt concentration. ß-CD thioethers show a 3-10 times higher binding potential than native ß-CD.

Liquid Structure Scenario of the Archetypal Supramolecular Deep Eutectic Solvent: Heptakis(2,6-di-O-methyl)-ß-cyclodextrin/levulinic Acid.

The concept of supramolecular solvents has been recently introduced, and the extended liquid-state window accessible for mixtures of functionalized cyclodextrins (CDs) with hydrogen bond (HB) donor species, e.g., levulinic acid, led to the debut of supramolecular deep eutectic solvents (SUPRA-DES). These solvents retain CD's inclusion ability and complement it with enhanced solvation effectiveness due to an extended HB network. However, so far, these promising features were not rationalized in terms of a microscopic description, thus hindering a more complete capitalization. This is the first joint experimental and computational study on the archetypal SUPRA-DES: heptakis(2,6-di-O-methyl)-ß-CD/levulinic acid (1:27). We used X-ray scattering to probe CD's aggregation level and molecular dynamics simulation to determine the nature of interactions between SUPRA-DES components. We discover that CDs are homogeneously distributed in bulk and that HB interactions, together with the electrostatic ones, play a major role in determining mutual interaction between components. However, dispersive forces act in synergy with HB to accomplish a fundamental task in hindering hydrophobic interactions between neighbor CDs and maintaining the system homogeneity. The mechanism of mutual solvation of CD and levulinic acid is fully described, providing fundamental indications on how to extend the spectrum of SUPRA-DES combinations. Overall, this study provides the key to interpreting structural organization and solvation tunability in SUPRA-DES to extend the range of sustainable applications for these new, unique solvents.

A High-Throughput Experimental Approach to Screening Gas Sorption by Liquids and Solids.

High-precision measurement of gas uptake from single or mixed feeds in solid and liquid sorbents traditionally requires time-consuming experimental procedures and/or complex and costly equipment. A simple and cost-effective headspace gas chromatography (HS-GC) approach for the fast, universal experimental screening of sorbents for gas uptake and/or determination of their real gas separation selectivity has been developed and is demonstrated for pressures up to 2500 mbar and temperatures above 30 °C. This method allows screening of solids and both volatile and nonvolatile liquid materials, physisorbents, and chemisorbents using both single and mixed permanent gases that can include CO2, CH4, H2, and NH3, for gas uptakes as low as 0.04 mmol or 1.8 mg of CO2. We estimate that this method allows for the screening of at least 30-96 sorbents (in triplicate) or 90-264 sorbents (singles) per day, representing at least a 90-3000 times reduction in the time required for equivalent analysis.

Encapsulation of Rosmarinus officinalis essential oil and of its main components in cyclodextrin: application to the control of the date moth Ectomyelois ceratoniae (Pyralidae).

BACKGROUND: Synthetic insecticides are the most useful tools for preventing losses caused by insect pest's infestation during storage. However, the use of pesticides should be limited because of the development of insect resistance and their adverse effects on human health and environment. In the last decades, natural insecticidal products, principally essential oils (EOs) and their active components, exhibited potential alternatives for pest control. Nevertheless, due to their volatile nature, encapsulation could be considered as the most appropriate solution. Therefore, this work aims to investigate the fumigant ability of inclusion complexes of Rosmarinus officinalis EO and its major constituents (1,8-cineole, α-pinene and camphor) with 2-hydroxypropyl-beta-cyclodextrin (HP-ß-CD) against Ectomyelois ceratoniae (Pyralidae) larvae. RESULTS: The encapsulation within HP-ß-CD reduced greatly the release rate of the encapsulated molecules. Therefore, free compounds were more toxic than those encapsulated. Moreover, results revealed that encapsulated volatiles exhibited interesting insecticidal toxicity towards E. ceratoniae larvae. In fact, after 30 days mortality rates were 53.85, 94.23, 3.85 and 42.31% for α-pinene, 1,8-cineole, camphor and EO, respectively, encapsulated within HP-ß-CD. In addition, results showed also that 1,8-cineole free and encapsulated was more effective toward E. ceratoniae larvae than the other tested volatiles. Additionally, the HP-ß-CD/volatiles complexes exhibited best persistence compared to the volatiles components. The half-life of the encapsulated α-pinene, 1,8-cineole, camphor and EO (7.83, 8.75, 6.87 and 11.20 days) was significantly longer than that of the free ones (3.46, 5.02, 3.38 and 5.58 days). CONCLUSION: These results sustain the utility of R. officinalis EO and its main components encapsulated in CDs as treatment to stored-date commodities. © 2023 Society of Chemical Industry.

Cyclodextrin-based supramolecular low melting mixtures: efficient absorbents for volatile organic compounds abatement.

Cyclodextrins (CDs) and deep eutectic solvents (DESs) are emerging absorbent materials for the removal of volatile organic compounds (VOCs). In this study, we have used combination of modified CDs and levulinic acid to form four DESs analogs, referred to as supramolecular low-melting mixtures (LMMs), to study their absorption characteristics towards five VOCs, namely acetaldehyde, butanone, dichloromethane, thiophene, and toluene. The supramolecular LMMs showed up to 250-fold reduction in the vapor-liquid partition coefficients compared to water. The overall absorption capacity found to be synergistic and seemed to be dictated by the hydrophobicity of the VOCs. Toluene and dichloromethane were absorbed at 99 and 95% by the supramolecular LMMs, respectively, even at higher concentrations, with a linear relationship between the concentration and absorption capacity. The LMMs also retained their absorption capacities even after five absorption/desorption cycles.

Cyclodextrins: from solute to solvent.

A supramolecular solvent based on cyclodextrin (CD) is presented here for the first time. Indeed, a low melting mixture was obtained by mixing levulinic acid and a CD derivative, which retained its inclusion ability in the resulting solvent. This new system gives rise to a new family of solvents that could be called SUPRADES (supramolecular deep eutectic solvents).

Drug-in-hydroxypropyl-ß-cyclodextrin-in-lipoid S100/cholesterol liposomes: Effect of the characteristics of essential oil components on their encapsulation and release.

Drug-in-cyclodextrin-in-liposome (DCL) represents a very promising approach for preserving essential oil (EO) components, thereby extending their shelf life and activity. In this study, we examined the effect of chemical structure, octanol/water partition coefficient (log P), and Henry's law constant (Hc) on the encapsulation and the release of monoterpenes (eucalyptol, pulegone, terpineol, and thymol) and phenylpropenes (estragole and isoeugenol) from DCLs. Hydroxypropyl-ß-cyclodextrin/EO component (HP-ß-CD/EO component) inclusion complexes were prepared in aqueous solution and loaded into liposomes by the ethanol injection method. The phospholipid:cholesterol:EO component molar ratio determined for DCL structures was affected by characteristics of EO components. The presence of a propenyl tail or a hydroxyl group in the structure of EO component may improve its loading into DCLs. Furthermore, low encapsulation efficiency (EE) was obtained for DCLs exhibiting high cholesterol membrane content. In addition, a positive linear relationship was found between the loading ratio of monoterpenes into DCLs and their hydrophobic character expressed as log P. The release of components from DCLs was influenced by their EE into the formulations. Finally, DCL formulations retain considerable amounts of EO components after 10 months.

New generation of supramolecular mixtures: Characterization and solubilization studies.

In this work, a series of novel low melting mixtures (LMM) based on cyclodextrins (CD) and levulinic acid and inspired by the deep eutectic solvents (DES), were prepared. These supramolecular mixtures are the first reported CD-based mixtures that are liquid at room temperature. Density, viscosity and rheological measurements as well as differential scanning calorimetry and thermogravimetric analysis were performed to characterize these new LMM. Nuclear magnetic resonance (NMR) spectroscopy was used to monitor their stability. Furthermore, their ability to solubilize trans-anethole (AN) and related essentials oils were evaluated by static headspace-gas chromatography (SH-GC), in comparison with water. AN was up to 1300 times more soluble in the CD-based LMM than in water. Finally, multiple headspace extraction (MHE) was used to monitor the release of AN from these LMM. After 10 extractions, 20 to 40% of AN was released from the studied LMM, while 70% was released from water. The new CD-based LMM have potential applications for solubilization and delivery of poorly soluble drugs.

Cyclodextrin-membrane interaction in drug delivery and membrane structure maintenance.

Cyclodextrins (CDs) are cyclic oligosaccharides able to improve drug water solubility and stability by forming CD/drug inclusion complexes. To further increase drug entrapment and delay its release, the CD/drug inclusion complex can be embedded in the aqueous phase of a liposome, a lipid vesicle composed of phospholipid bilayer surrounding an aqueous compartment. The resulting carrier is known as drug-in-cyclodextrin-in-liposome (DCL) system. CDs and DCLs are recognized as effective drug delivery systems; therefore, understanding the interaction of CDs with liposomal and biological membranes is of great importance. CDs are able to extract phospholipids, cholesterol, and proteins from membranes; the effect depends on the membrane structure and composition as well as on the CD type and concentration. Under definite conditions, CDs can affect the membrane fluidity, permeability, and stability of liposomes and cells, leading to the leakage of some of their internal constituents. On the other side, CDs demonstrated their beneficial effects on the membrane structure, including preservation of the membrane integrity during freeze-drying. In this paper, we review the literature concerning the interaction of CDs with biomimetic and biological membranes. Moreover, the impact of CDs on the membrane properties, mainly fluidity, stability, and permeability, is highlighted.