Inclusion Complexes Research Articles

Exceptional stability of the sugammadex-solasodine complex: Insights from experimental and theoretical studies

Sugammadex (SGM) is the first cyclodextrin (CD)-based selective relaxant binding agent. We investigated its ability to capture natural aminosteroid phytotoxins, and assessed its potential as an antidote for intoxication. Solasodine (SS), a toxic alkaloid from the Solanaceae family, was chosen as the model compound. Complexation was studied using nuclear magnetic resonance (NMR) spectroscopy, molecular modelling, and isothermal titration calorimetry (ITC). NMR in various D2O/DMSO‑d6 media revealed a particularly stable inclusion-type complex, identifying a slow exchange process between the CD and the aminosteroid along with a less significant fast exchange between DMSO and SGM. Using various NMR techniques, the structure and kinetic/thermodynamic parameters of the inclusion complex were explored. Theoretical calculations showed the secondary amino head of SS near the carboxylate ends of the SGM sidechains, facilitating intermolecular ionic interactions. ITC experiments in an aqueous environment provided Ka stability constants of 7.03 × 106 M−1 and 4.17 × 106 M−1 at 25 °C and 37 °C, respectively, similar to previously reported SGM complexes with aminosteroid neuromuscular blockers. Finally, SGM significantly increased cell survival and reduced SS toxicity in mHippoE-14 mouse hippocampal embryonic cells, supporting the hypothesis that SGM could act as an antidote to SS's toxic effects.

Liquisolid Technique for Solubility Enhancement of Poorly Soluble Drug - A Brief Review.

Most of the newly discovered drug candidates are lipophilic and poorly water-soluble, making it a significant challenge for the pharmaceutical industry to formulate suitable drug delivery systems. This review gives insight into an overview of the liquisolid technique (LST) and summarizes the progress of its various applications in drug delivery. This novel technique involves converting liquid drugs or drugs in a liquid state (such as solutions, suspensions, or emulsions) into dry, nonadherent, free-flowing, and readily compressible powder mixtures by blending or spraying a liquid dispersion onto specific powder carriers and coating materials. In Liquisolid systems, the liquid medication is absorbed into the interior framework of carriers. Once the carrier's interior is saturated with liquid medication, a liquid layer forms on the surface of the carrier particles, which is instantly adsorbed by the fine coating material. As a result, a dry, free-flowing, and compressible powder mixture is formed. Compared to other solubility enhancement techniques, s.a. micronization, inclusion complexation, microencapsulation, nanosuspension, and self-nano emulsions, LST is relatively simple to prepare and may offer a cost-effective solution to enhance the solubility of poorly water-soluble drugs enhancing its bioavailability in drug formulation and delivery.

The mechanochemical and supercritical fluid synthesis of β-cyclodextrin-hesperidin inclusion complex: A comparison green chemistry versus lyophilization

Hesperidin is a rutinoside of flavanone type with relevant therapeutic properties but poor water solubility which limits its therapeutic applicability. However, cyclodextrins (CDs) have been successfully used as drug carriers to enhance the solubility of several drugs, to improve their bioavailability, and therapeutic efficacy. We report herein the formation of inclusion complexes of β-cyclodextrin and hesperidin through the green approaches mechanochemistry and supercritical fluid and compare these results versus the classical lyophilization method. The resulting stoichiometries and the specific interactions of the complexes were analyzed by NMR, UV, and mass spectrometry. The β-cyclodextrin and hesperidin inclusion complex (IC) successfully obtained through green methodologies demonstrated superior levels of flavonoid content. In terms of solubility, the mechanochemistry inclusion complex showed the best improvement in solubility. We demonstrate herein that the use of green methodologies such as supercritical fluids and mechanochemistry are useful alternatives to the conventional method of lyophilization, to improve the solubility of β-cyclodextrin IC.

Биологически активные гидролизаты белков молока и их комплексы включения с циклодектринами

Enzymatic hydrolysis of dairy proteins increases their nutritional and biological value while reducing their allergenic potential. The subsequent complexation of peptides with cyclodextrins (CDs) reduces the bitterness of the hydrolyzed proteins. The research objective was to obtain hydrolysates of whey proteins and their cyclodextrin inclusion complexes with peptides, as well as to describe the peptide composition of the cleaved dairy proteins, biological activity, and sensory profile of the hydrolysates and inclusion complexes. The research featured enzymatic whey protein hydrolysates with an extensive hydrolysis degree and their inclusion complexes with β- and γ-CDs. Dairy proteins were hydrolyzed with alcalase, and the hydrolysates obtained were subjected to micro- and ultrafiltration (cut-off limit – 10 kDa). The peptide composition of the hydrolyzed proteins was determined by the methods of high-performance liquid chromatography and chromatography-mass spectrometry. The antimutagenic activity was evaluated using the Ames test whereas the antibacterial effect was studied with the impedimetric method. The antioxidant activity was detected with fluorimetry and spectrophotometry. The method of competitive enzyme immunoassay was applied to reveal the antigenic properties. The bitterness of the experimental sample s was determined by a sensory evaluation. The research delivered the optimal modes for whey protein cleavage with alcalase that made it possible to achieve efficient micro- and ultrafiltration. The resulting hypoallergenic peptide fractions and their inclusion complexes with β- and γ-CDs possessed antioxidant, antibacterial, and antimutagenic properties. The whey proteolysis and subsequent filtration with/without tindalization demonstrated a 265/589-fold decrease in the residual antigenicity. The fluorimetric method showed a 1.79/1.90-fold increase in the antioxidant activity of the hydrolysate in complexes with β- and γ-CDs. Binding of β-CDs to peptides enhanced their antimicrobial activity against Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 6538. The hydrolysate samples with β-CDs showed less bitterness. Whey proteolysis with alcalase under optimized conditions and subsequent fractionation resulted in a product with high consumer qualities. Enzymatic hydrolysates of dairy proteins and their CD inclusion complexes were able to substitute native protein components. Their bioactive properties, good taste, and low allergenic potential mean good prospects for the functional food industry.

Eco-Friendly Microwave Synthesis of Sodium Alginate-Chitosan Hydrogels for Effective Curcumin Delivery and Controlled Release.

In this study, we developed sodium alginate-chitosan hydrogels using a microwave-assisted synthesis method, aligning with green chemistry principles for enhanced sustainability. This eco-friendly approach minimizes chemical use and waste while boosting efficiency. A curcumin:2-hydroxypropyl-β-cyclodextrin complex was incorporated into the hydrogels, significantly increasing the solubility and bioavailability of curcumin. Fourier Transform Infrared Spectroscopy (FTIR) analysis confirmed the structure and successful incorporation of curcumin, in both its pure and complexed forms, into the polymer matrix. Differential scanning calorimetry revealed distinct thermal transitions influenced by the hydrogel composition and physical cross-linking. Hydrogels with higher alginate content had higher swelling ratios (338%), while those with more chitosan showed the lowest swelling ratios (254%). Scanning Electron Microscopy (SEM) micrographs showed a porous structure as well as successful incorporation of curcumin or its complex. Curcumin release studies indicated varying releasing rates between its pure and complexed forms. The chitosan-dominant hydrogel exhibited the slowest release rate of pure curcumin, while the alginate-dominant hydrogel exhibited the fastest. Conversely, for curcumin from the inclusion complex, a higher chitosan proportion led to the fastest release rate, while a higher alginate proportion resulted in the slowest. This study demonstrates that the form of curcumin incorporation and gel matrix composition critically influence the release profile. Our findings offer valuable insights for designing effective curcumin delivery systems, representing a significant advancement in biodegradable and sustainable drug delivery technologies.

Influence of incorporating beta-cyclodextrin/essential oil-based wood preservative on the bonding strength of wood composite products

The introduction of additives during the production of wood composites may disrupt the development of bonding strength between wood and adhesive, potentially compromising the structural performance of wood composites. This study investigates the impact of incorporating a natural wood preservative into 3-ply southern yellow pine (SYP) plywood on its bonding strength. The formation of β-cyclodextrin and trans-cinnamaldehyde (βCD-tCN) inclusion complex as a natural wood preservative was confirmed by Fourier transform infrared and X-ray diffraction analyses, with an inclusion yield ranging 78 % to 120 %. The differential scanning calorimetry analysis found the curing of pMDI with wood was not significantly affected by the βCD-based additives. The influence of βCD-tCN addition on the bonding strength of a wood composite was assessed by a shear strength test of the 3-ply plywood, following ASTM D906-20. The average shear strength of all panels ranged 1.53 N/mm2 to 2.07 N/mm2, exceeding the minimum requirement of 1.00 N/mm2 for cross-layer bond lines according to EN 16351-2015. Statistical analysis indicated no significant differences between the bonding strength of pristine pMDI and pMDI containing βCD-tCN complex. The combined results suggest that βCD-tCN could be effectively implemented in the manufacturing of wood composite products.

Antioxidant films loaded with β-cyclodextrin-quercetin for enhancing food preservation

As the improvement of consciousness of environment, a considerable effort has been made to shift from petroleum-based plastics to biodegradable alternatives, especially in the food packaging industry. In this work, we develop an innovative food packaging film by encapsulating quercetin (Que) within β-cyclodextrin (β-CD) to create β-CD-Que inclusion complexes, which are then dispersed in a matrix of tragacanth gum (TG) and carboxymethyl chitosan (CMCS) using a solution casting technique. β-CD-Que inclusion complexes were characterized using various methods, including 1H NMR, 2D ROESY and phase solubility testing, to elucidate the interaction between Que and β-CD. ATR–IR, X-ray diffraction, and SEM were employed to confirm the uniform dispersion of β-CD-Que within the macromolecular substrate. The incorporation of β-CD-Que considerably improves the mechanical properties of films, increasing the elongation at break from 13.68 % to 25.74 %. Rheological tests demonstrate that the viscosity of the film-forming complex solution became larger. The films were demonstrated to reduced water vapor and oxygen permeability, possessing remarkable antioxidant capability evidenced by DPPH and ABTS radical scavenging rates of 78.01 % and 99.59 %, respectively. The TG/CMCS/β-CD-Que composite film shows excellent potential for food packaging and preservation applications.

Development of apple pectin/chitosan-based active films integrated with apple polyphenol/hydroxypropyl-β-cyclodextrin inclusion complex for pork preservation

Sustainable bio-based active films are promising alternative materials that can alleviate the growing environmental problems. Apple processing generates a large number of by-products rich in pectin and polyphenols. Herein, we extracted apple pectin (Apec) from apple pomace, developed a multifunctional bilayer film based on Apec and chitosan by incorporating inclusion complex of apple polyphenol and hydroxypropyl-β-cyclodextrin (ICAH). The results showed that the incorporation of ICAH remarkably improved the mechanical strength, barrier properties, and the thermal stability of the films. Meanwhile, the composite films loaded with ICAH exhibited potent antioxidant and antibacterial activities in vitro. Furthermore, a 7-day shelf-life analysis on fresh pork verified that the films were effective in maintaining the pH level (below 6.0), reducing the thiobarbituric acid reactive substance (from 1.18 to 0.63 mg MDA/kg) and total volatile basic nitrogen (from 23.27 to 14.03 mg/100 g), and inhibiting the microbial growth (from 6.83 to 3.74 log CFU/g), thereby obtaining a satisfactory sensory evaluation. The pork wrapped with the films can significantly extend the period of freshness from 4 days to 7 days under refrigeration at 4 °C. The results suggest that the prepared composite films hold promise as an active packaging material for application in pork preservation.

Chiral discrimination during photoinduced electron transfer from L/D-tryptophan to electron-excited uranyl ion as a part of UO22+ ⊂ α–CD inclusion complex

Spectral-luminescent research indicates the formation of inclusion complexes during the interaction of uranyl nitrate and α–cyclodextrin (α–CD) in aqueous solutions. The chiral α–CD matrix imparts optical activity to the electronically excited uranyl ion *UO22+aq in the clathrate, which manifests itself in the chiral discrimination of the quenching of *UO22+aq by tryptophan enantiomers. It was found that the Stern-Volmer constant for D–Trp is 1.8 ± 0.2 times higher than that for L–Trp. A mechanistic explanation for the observed effect is proposed by DFT calculations.

Alginate-based edible coating with magnoliae essential oil/β-cyclodextrin inclusion complex for Kyoho grape preservation

To prolong the shelf life of Kyoho grapes at room temperature, an edible coating composed of sodium alginate (SA) containing an inclusion complex of Magnoliae essential oil (MEO) and β-cyclodextrin (β-CD) (SA/MEO@β-CD coating) was developed. Initially, the inclusion complex of MEO with β-CD was developed to enhance its thermal stability. MEO@β-CD was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). In addition, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) results show that β-CD can improve the thermal stability of MEO. The entrapment efficiency and loading efficiency were 82.56% and 8.8%. MEO@β-CD was added to the SA coating for preserving Kyoho grapes, while monitoring the enzyme activity, total bacterial count, and sensory characteristics of the grapes. Compared to the uncoated group, the SA/MEO@β-CD coated group exhibited a significant reduction in total color difference, decay rate, weight loss rate, enzyme activity, and total number of bacterial colonies, while also slowing the decline in hardness and total soluble solids. The effect of the SA/MEO@β-CD1 group was highly effective. Conclusively, the SA/MEO@β-CD coating preserves Kyoho grapes by reducing lipid oxidation and inhibiting microbial growth, demonstrating its potential as an advanced edible packaging solution for grape preservation.

Starch-calcium inclusion complexes: Optimizing transparency, anti-fogging, and fluorescence in thermoplastic starch

With the increasing demand for anti-fogging transparent material and environmental concern, developing sustainable intrinsically hydrophilic and anti-fogging thermoplastic material is important. In this work, thermoplastic starch (TPS) films with good anti-fogging and optical properties were prepared via coordinative interactions with calcium chloride (CaCl2), zinc chloride (ZnCl2) and magnesium chloride (MgCl2). Among them, TPS with the incorporation of CaCl2 exhibited excellent anti-fogging and high optical transparency. Notably, the haze of TPS-0.2Ca just increased from 2.5 % to 3.8 %, with transparency remaining robust at 80 %. FTIR, XPS and 2D-WAXD results demonstrated the formation of inclusion complexes between Ca2+ and hydroxyl groups, which could modulate the hydrophobicity and hydrophilicity of TPS. Moreover, DMA, POM, and AFM results revealed that the formation of starch-calcium inclusion complex was crucial for achieving uniform intensity distribution, reduced crystalline areas, minimized light scattering, and decreased surface roughness, thereby contributing to the high transparency and low haze of TPS-Ca. Furthermore, TPS-Ca samples exhibited inherent fluorescent properties under UV light, showing the potential as disposable and eco-friendly fluorescence materials. This work provides new insights into design of sustainable TPS-based materials that combine robust antifogging performance with advanced optical property.

Synthesis and characterization of self-healable supramolecular hydrogel based on carboxymethyl cellulose for biomedical applications

Hydrogels have been widely used in biomedical fields including tissue engineering, drug delivery and cell delivery and 3D cell delivery due to abundant water content in their hydrophilic three-dimensional networks and having soft tissue similar to the human body. In recent years, supramolecular hydrogels (SHG) formed by the inclusion complex between polyethylene glycol (PEG) and macrocycles such as cyclodextrin (CD) have attracted much interest due to their excellent biocompatibility and great potential in biomedical. In this research, a carboxymethyl cellulose (CMC)-based graft copolymer was prepared by using acrylic acid (AA) and maleic anhydride functionalized β-CD (β-CD-MA) as comonomers and ammonium persulfate (APS) as initiator. Then, a self-healable supramolecular hydrogel was synthesized by formation of a host-guest inclusion complex between CMC-g-poly (AA-co-β-CD-MA) as host molecule and cytosine- and guanine-modified PEG as guest molecules. The prepared hydrogel was characterized by Scanning Electron Microscope (SEM), X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Nuclear magnetic resonance spectroscopy (1H NMR). The thermal stability of hydrogel was also determined by thermal gravimetric (TGA) and differential scanning calorimetry (DSC) methods. In addition, the loading and release profiles of metformin hydrochloride (MH) drug as a model on hydrogel was investigated. The results indicated that the drug release from the hydrogel peaks around 360 min and aligns with the Ritger-Peppas model. The hydrogel's self-healing property was examined at ambient temperature and 37 °C. It showed 70 % healing in 1.5 h and completed recovery after 9 h.

PCL/soy peptide nanofibers incorporated with riboflavin/HP-β-CD assemblies for improving fruit storage quality

In this study, we first successfully developed functionalized electrospun nanofibers (PCL/SP/ICs) loaded with Riboflavin (RF) for fruit preservation with inclusion complexes (RF/HP-β-CD, IC) formed by encapsulating RF with hydroxypropyl-β-cyclodextrin (HP-β-CD) as a core material and soy peptide-assisted polycaprolactones (PCL/SP) as an overwrap material. Compared to 1 wt% and 5 wt% IC, nanofibers implanted with 3 wt% IC had an acceptable water contact angle (87.40°), good thermal stability, and superior mechanical properties. Also, RF/HP-β-CD integration conferred antimicrobial and antioxidant capabilities to PCL/SP fiber membranes. High-performance liquid chromatography (HPLC) studies revealed that produced films of PCL/SP/ICs could continuously and controllably release RF (within 200 h), hence retarding grape degradation and decreasing mass loss rate and titratable acid content throughout an 8-day storage period. Based on these findings, electrospun nanofiber films may be useful for vitamin loading in active food packaging.

Edible thermosensitive chitosan/hydroxypropyl β-cyclodextrin hydrogel with natural licoricidin for enhancing oral health: Biofilm disruption and demineralization prevention

Dental caries, a widespread and significantly detrimental health condition, is characterized by demineralization, pain, compromised tooth functionality, and various other adverse effects. Licoricidin (LC), a natural isoflavonoid, demonstrates potent antimicrobial properties for maintaining oral health. However, its practical application is significantly hindered by its limited water solubility and susceptibility to removal within the oral environment. To tackle this issue, we developed a delivery oral system by an edible thermosensitive chitosan- disodium beta-glycerol phosphate pentahydrate (CS/β-GP) hydrogel to load LC/Hydroxypropyl beta-cyclodextrin (HP-β-CD) inclusion complexes. These hydrogels (LC/HP-β-CD/CS/β-GP) could solidify rapidly at oral temperature and sustainably release LC, thereby preventing its rapid clearance from the oral cavity. We confirmed the significant antibacterial activity of this hydrogel against Streptococcus mutans and Staphylococcus aureus. Additionally, the HP-β-CD combination enhanced LC to penetrate bacterial biofilms and inhibit biofilm growth, leading to leakage of cellular proteins and DNA. Additionally, we studied the effect of LC/HP-β-CD/CS/β-GP on intracellular ROS levels and MMP, comprehensively exploring its antimicrobial mechanism. Furthermore, LC/HP-β-CD/CS/β-GP exhibited the ability to inhibit demineralization and demonstrated excellent biocompatibility. In summary, this study presented a safer approach to oral delivering bioactive substances, offering a promising strategy for enhanced oral health and safety.

Microwave-assisted, sulfhydryl-modified β-cyclodextrin-silymarin inclusion complex: A diverse approach to improve oral drug bioavailability via enhanced mucoadhesion and permeation

The current study aimed to generate a sulfhydryl-modified β-cyclodextrin-silymarin complex (sulfhydryl-modified β-CD-SMN complex) and to evaluate the enchantment in solubility, permeability, and bioavailability of a model BCS Class IV drug silymarin (SMN). For this purpose, sulfhydryl-modified β-CD was synthesized by replacing all primary and secondary –OH groups at the β-CD backbone with sulfhydryl groups via a novel microwave-assisted technique. Afterward, sulfhydryl-modified β-CD was complexed with silymarin and characterized by FTIR and 1H NMR spectroscopy. Moreover, no. of sulfhydryl groups and their oxidative stability, solubility, safety, mucoadhesion, release, diffusion, and rheological studies were performed. Furthermore, in-vivo studies were conducted to confirm enhanced pharmacokinetic properties of silymarin. Sulfhydryl-modified β-CD showed 8291 ± 418 μmol/g sulfhydryl groups that were prone to oxidation at pH ≥ 5, however, most of the sulfhydryl groups were found stable at pH 4 having a pKa value of 8.3. Modified β-CD oligomer showed improved solubility of SMN, significantly enhanced drug transport across goat intestinal mucosa, 78-fold improved mucoadhesion, improved drug dissolution and 4.4-fold enhanced dynamic viscosity. No toxic effects were reported to Caco-2 cells at 0.5 % (m/v) concentration of sulfhydryl-modified β-CD for 24 h. The apparent permeability coefficient (Papp) of SMN was 6.9-fold enhanced on goat intestinal mucosa. Moreover, in-vivo studies confirmed a significantly enhanced oral bioavailability of SMN due to combination with sulfhydryl-modified β-CD. Based on these findings, the sulfhydryl-modified β-CD-silymarin inclusion complex can be a promising technique to enhance the bioavailability of BCS Class IV drugs via enhanced solubility, mucoadhesion, and permeability triple action.

A Highly Sensitive Inclusion Complex Based Spectrofluorimetric Method for the Determination of Certain Sodium Glucose Cotransporter-2 Inhibitors: Greenness Assessment and Application to Different Biological Fluids.

This study introduces a remarkably simple, green, and highly sensitive inclusion complex based spectrofluorimetric method for analyzing two sodium glucose cotransporter-2 (SGLT2) inhibitors: empagliflozin (EGF) and dapagliflozin (DGF). The method utilizes beta-cyclodextrin (β-CD) complexation to enhance the native fluorescence of EGF and DGF in aqueous solutions, resulting in 11.0-fold and 9.0-fold intensity increases, respectively. Fluorescence measurements were conducted at 301 nm emission following 230 nm excitation for both drugs. The method demonstrates excellent linearity (0.9994 for EGF and 0.9993 for DGF) over concentration ranges of 5.0-250.0 ng/mL and 10.0-300.0 ng/mL, with low detection limits of 1.05 and 1.38 ng/mL for EGF and DGF, respectively. The method's versatility was validated through successful application in pharmaceutical formulations, content uniformity testing, and biological fluids. This eco-friendly approach primarily uses water as a solvent and requires minimal reagents. The method's environmental impact was comprehensively evaluated using the analytical eco-scale, green analytical procedure index (GAPI), and analytical greenness metric (AGREE).

Effect of inclusion complex formation and mechanoactivation on the structure and rheological behavior of starch-oleic acid mixtures

In the present work, for the first time, mechanical activation implemented in a rotor-stator device (RSD) has been used to enhance the formation of the amylоse-fatty acid complex in gelatinized starch at a moderate temperature (40 °C) using oleic acid (ОА) as a model guest compound. Mechanical activation was found to cause an increase in the complexing index from 10 to 30 % for non-activated mixtures to 83–92 %. The study of aqueous and dried starch-OA mixtures using optical and AFM microscopy and dynamic light scattering methods revealed a uniform distribution of amylose-OA complex particles with a size of 125–260 nm in the starch matrix. The freeze-dried starch-ОА sample prepared using mechanical activation exhibited a V-type crystalline structure. By rotational viscometry and dynamic rheometry, it was found that mechanical activation causes the gelation of aqueous starch-OA mixtures, which accompanies a decrease in their fluidity and an increase in elasticity. The developed method can be recommended for large-scale production of thickening and texture modifying materials based on gelatinised starch containing a fatty acid as a nutritional or structuring additive.

Physicochemical Properties of Betacyclodextrin-Assisted Extracts of Green Rooibos (Aspalathus linearis)

Betacyclodextrin (β-CD)-assisted extracts of green rooibos displayed elevated polyphenolic content and antioxidant activity compared with aqueous extracts. This study aimed to analyse the physicochemical properties of aqueous green rooibos and 15 Mm β-CD at 40 °C for 60 min. Sorption isotherms and colour (L*a*b*C*) were evaluated. Thermogravimetric analysis and Fourier transform infrared were conducted to verify encapsulation. Sorption isotherm studies revealed that β-CD reduced water uptake, resulting in a reduction in the monolayer value of GRE (7.90) to 6.40 for β-GRE. Betacyclodextrin contributed to increased lightness (L*) and decreased redness (a*) of green rooibos. However, storing extracts at varied water activity resulted in a reduction in L* and chroma (C*), with a higher reduction observed for GRE than β-GRE. Thermogravimetric analysis revealed that GRE degraded at 180 °C, followed by β-GRE at 260 °C and β-CD at 340–375 °C. Betacyclodextrin increased the thermal stability of green rooibos; as a result, β-GRE displayed a superposition of GRE and β-CD in its thermogram, confirming the formation of inclusion complexes. Fourier transform infrared spectra indicated the disappearance or shifting of characteristic peaks, with the formation of hydrogen bonds between GRE and β-CD at the 1255 cm−1 band depicting C–O stretching of carboxylic acid.

Intestinal-Targeted Digestion of Heme Chloride by Forming Inclusion Complexes In Vitro.

Hemin, a heme-like compound with significant biological activity, shows promise as an iron supplement for humans. Nonetheless, its poor solubility in water greatly impedes its absorption and utilization. To surmount this obstacle, researchers have chosen various cyclodextrins with distinct cavity sizes and derivative groups to act as hosts, forming inclusion complexes with hemin chloride. Among these, γ-cyclodextrin has been identified as the optimal carrier, based on a thorough evaluation of its encapsulation efficiency, solubility, and molecular docking. Multiple characterization techniques further confirmed the formation of these inclusion complexes. Results from IEC-6 cell experiments indicated that the cytotoxicity of the inclusion complexes was lower than that of FeSO4. Static and dynamic gastrointestinal simulation digestion systems were established, and the results showed that the bioavailability of the inclusion complex was significantly higher than that of raw hemin. Additionally, only about 0.29% of hemin chloride is digested by gastric enzymes, whereas 9.52% is digested by pancreatic enzymes in the static gastrointestinal simulation digestion system, with similar outcomes observed in the dynamic system. These findings suggest that targeted digestion in the intestine significantly enhances the bioavailability of hemin chloride by forming inclusion complexes in vitro.

Functionalized composite nanofiber membranes for selective steroid hormone micropollutants uptake from water: Role of cyclodextrin type

Cyclodextrins (CD) entrapped in nanofiber composite membranes are potential selective adsorbing materials to remove steroid hormone (SHs) micropollutants from water. This study aims to elucidate the role of CD macrocyclic host type on the SHs inclusion complexation and uptake in filtration. Three CD types (α, β, and γ) are cross-linked with epichlorohydrin to form polymers (αCDP, βCDP and γCDP) and entrapped into a nanofiber composite membrane by electrospinning. TGA analysis confirmed the CD entrapment into the nanofiber without loss of CD molecules during filtration.The CD type plays a dominant role in controlling the removal of different SHs. A similar removal (range 33 to 50 %) was observed with αCDP, irrespective of the SH type. In contrast, removal and uptake dependent on SH type were observed for β and γCDP, with the highest removal of 74 % for progesterone, followed by estradiol (46 %) and estrone (27 %) and the lowest removal of 3 % for testosterone.Molecular dynamic (MD) simulation revealed a stronger and more stable complex formed with βCDP, as demonstrated by: i) the closer spatial distribution of SH molecules from the βCDP cavity and, ii) the quantum chemistry calculations of the lower de-solvation energy (+6.0 kcal/mol), which facilitates the release of water molecules from interacting interface of CD molecule and hormone. Regarding γCDP, the highest de-solvation energy (+8.3 kcal/mol) poses an energetic barrier, which hinders the formation of the inclusion complex. In the case of αCDP, a higher interaction energy (-8.9 kcal/mol) compared to βCDP (-4.9 kcal/mol) was obtained, despite the broader spatial distribution observed from the MD simulation attributed to a dominant hydrogen bonding interaction with the OH primary groups on the external surface cavity.The findings highlight the relevance of the CD type in designing selective adsorbing membranes for steroid hormone micropollutant uptake. Experimental results and MD simulation suggest that βCD is the most suitable CD type for steroid hormone uptake, due to a more stable and stronger inclusion complexation than α and γCD.