Formation Of Inclusion Complexes Research Articles

Fabrication of biocompatible water-soluble supramolecular nanofibers of oseltamivir with methyl-β-cyclodextrin for enhanced drug release

In recent times, there has been a growing interest in the advancement of nanofiber technology using materials based on cyclodextrin (CD). This heightened interest is primarily driven by their potential applications in controlled drug release. This research aims to create the nanofibers (NF) which involves incorporating an antiviral agent, oseltamivir (OTV) into the CD cavity, forming inclusion complexes (IC) that greatly improve drug encapsulation efficiency. To assess the physicochemical properties and drug-loading capabilities of these CD-based NF, a variety of characterization techniques can be utilized. It is noteworthy that NF containing OTV:MCD-IC/PVA demonstrates a continuous release of OTV (89.25%) at acidic conditions (pH 5.8) when compared to NF holding no MCD materials. Moreover, dissolution studies reveal that the resulting material is non-toxic and readily soluble in water (less than 2 min). MTT assay indicated that the examined NF are completely safe and do not have/make any adverse effects on the cells (cell viability is more than 98%). The fibroblast cells grown on nanomatrixes composed of both OTV/PVA and OTV:MCD IC/PVA NF did not display any indications of apoptosis or nuclear shrinkage. The development of such systems holds significant promise for advancing therapeutic strategies in the management of viral infections.

Host–Guest Interaction Study of Olmesartan Medoxomil with β-Cyclodextrin Derivatives

Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated β-cyclodextrin (RM-β-CD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG—thermogravimetry; DTG—derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host–guest system OLM/RM-β-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-β-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.

Inclusion Complexes of Ethanamizuril with β- and Hydroxypropyl-β-Cyclodextrin in Aqueous Solution and in Solid State: A Comparison Study

Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, we performed molecular docking and then systematically compared the interactions of EZL with β-CD and HP-β-CD in both aqueous solution and the solid state, aiming to elucidate the solubilization effect and mechanism of cyclodextrins (CDs). The interactions were also examined in the solid state using DSC, PXRD, and FT-IR. The interactions of EZL with CDs in an aqueous solution were investigated using PSA, UV-vis spectroscopy, MS, 1H NMR, and 2D ROESY. The results of phase solubility experiments revealed that both β-CD and HP-β-CD formed inclusion complexes with EZL in a 1:1 molar ratio. Among them, HP-β-CD exhibited higher Kf (stability constant) and CE (complexation efficiency) values as well as a stronger solubilization effect. Furthermore, the two cyclodextrins were found to interact with EZL in a similar manner. The results of our FT-IR and 2D ROESY experiments are in agreement with the theoretical results derived from molecular simulations. These results indicated that intermolecular hydrogen bonds existing between the C=O group on the triazine ring of EZL and the O-H group of CDs, as well as the hydrophobic interactions between the hydrogen on the benzene ring of EZL and the hydrogen of CDs, played crucial roles in the formation of EZL/CD inclusion complexes. The results of this study can lay the foundation for the future development of high-concentration drinking water delivery formulations for EZL.

Complex formation with modified cyclodextrins for improving biopharmaceutical properties of baricitinib, a novel immunomodulatory drug

Baricitinib is an orally active drug that has recently been approved by FDA and EMA for the treatment of rheumatoid arthritis, alopecia areata, COVID-19 and other inflammatory diseases. The application of baricitinib is limited by its poor aqueous solubility. In this context, this work aims to improve the pharmacologically important properties of baricitinib through inclusion complex formation with modified cyclodextrins. For the first time, the complexation of baricitinib with modified cyclodextrins in aqueous solutions was studied using 1H NMR, capillary electrophoresis, and isothermal saturation method. Thermodynamic parameters of the complexation of the modified cyclodextrins with different ionized forms of baricitinib were obtained and analyzed. The impact of the nature of cyclodextrin substituents and the degree of ionization of baricitinib on the inclusion complex formation and solubilization is considered. The increase in baricitinib solubility in the presence of the modified cyclodextrins is accompanied by a decrease in the membrane permeability of the drug. It was shown that concentration dependences of the permeability coefficient can be used to predict the binding constants of baricitinib with cyclodextrins and the solubility-permeability interplay.

Direct electrospinning for producing multiple activity nanofibers consisting of aggregated luteolin/hydroxypropyl-gamma-cyclodextrin inclusion complex

Hydroxypropyl-gamma-cyclodextrin (HPγCD) inclusion complex nanofibers (Lut/HPγCD-IC-NF) containing Luteolin (Lut) were prepared by electrospinning technology. Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) spectra confirmed the formation of Lut/HPγCD-IC-NF. Scanning electron microscopy (SEM) images showed that the morphology of Lut/HPγCD-IC-NF was uniform and bead-free, suggesting that self-assembled aggregates, macromolecules with higher molecular weights, were formed by strong hydrogen bonding interactions between the cyclodextrin inclusion complexes. Confocal laser scanning microscopy (CLSM) images showed that Lut was distributed in Lut/HPγCD-IC-NF. Proton nuclear magnetic resonance (1H NMR) spectroscopy revealed the change in chemical shift of the proton peak between Lut and HPγCD, confirming the formation of inclusion complex. Thermogravimetric analysis (TGA) proved that Lut/HPγCD-IC-NF had good thermal stability. The phase solubility test confirmed that HPγCD had a solubilizing effect on Lut. When the solubility of HPγCD reached 10 mM, the solubility of Lut increased by 15-fold. The drug loading test showed that the content of Lut in fibers reached 8.57 ± 0.02 %. The rapid dissolution experiment showed that Lut/HPγCD-IC-NF dissolved within 3 s. The molecular simulation provides three-dimensional evidence for the formation of inclusion complexes between Lut and HPγCD. Antibacterial experiments showed that Lut/HPγCD-IC-NF had enhanced antibacterial activity against S. aureus. Lut/HPγCD-IC-NF exhibited excellent antioxidant properties with a free radical scavenging ability of 89.5 ± 1.1 %. In vitro release experiments showed Lut/HPγCD-IC-NF had a higher release amount of Lut. In conclusion, Lut/HPγCD-IC-NF improved the physicochemical properties and bioavailability of Lut, providing potential applications of Lut in the pharmaceutical field.

Enhanced Solubility and Oral Bioavailability of Niclosamide- Sulfobutylether-β-Cyclodextrin Sodium Inclusion Complexes: An Approach to Improve its Repurposing Potential

Niclosamide monohydrate (NCL) displays promising efficacy across diverse medical conditions, but its limited solubility (1.6µg/ml at 20°C) and oral bioavailability (10%) hinder its translational potential. In this study, we investigate the complexation of NCL with sulfobutylether-β-cyclodextrin sodium (SBECD) as a strategy to enhance its solubility, dissolution rate and oral bioavailability. Molecular docking studies revealed weak binding (∆Gbind < 2.0kcal/mole) between NCl and SBECD. The nitrophenyl ring inserted into the SBECD cavity, while the phenyl ring, housing Cl and OH groups, prominently extended outside. Phase solubility studies confirmed a 1:1 inclusion complex formation with a stability constant of 186M-1. Inclusion complexes, prepared via co-grinding, kneading, solvent evaporation, and spray drying, significantly improved NCL dissolution. Specifically, the spray dried and kneaded complexes achieved complete drug release within 60minutes, unlike pure NCL exhibiting only 16% dissolution at 90minutes. Microscopic analysis showcased reduced particle surface area in the spray dried complex. Oral bioavailability assessments demonstrated an approximately1.6-fold increase for the spray dried and kneaded complexes compared to pure NCL. Our findings support the scalability and efficacy of NCL-SBECD complexation as a strategic approach for enhancing the repurposing potential of NCL in therapeutic applications.

Molecular encapsulation of the protocatechuic and vanillic acid derivatives with β-cyclodextrin: Structural determination, antibacterial assessment, and molecular docking analysis

The phenolic chemical framework represents one of the most utilized structural motifs in the pursuit of innovative biologically active compounds. Particularly, the urgency for efficient antibacterial agents is still ongoing, especially due to rising bacterial resistance to common therapeutics. The physicochemical profile and efficiency of bioactive agents could be enhanced by their inclusion with cyclodextrins. In this study, the encapsulation of four protocatechuic and vanillic acid derivatives was performed in the reactions with β-cyclodextrin. The host-guest interactions and the formation of inclusion systems were confirmed by NMR, IR, and XRPD spectra. The Job's plot assay revealed the 1:1 stoichiometric ratio in the formed inclusion complexes, whereas the molecular docking analysis exposed the most favorable inclusion modes of guest molecules within the β-cyclodextrin cavity. The in vitro antibacterial investigations performed on selected G+ and G− bacteria revealed significantly enhanced activity of inclusion complexes in comparison to guest molecules. In general, the tested substances exhibited antibacterial activity with the MIC50 values determined in the range of 0.20–7.98 mM. Here, L. monocytogenes (G+) and E. coli (G−) strains were most sensitive to the treatment with guests and inclusion complexes. In several cases, the investigated compounds exerted comparable or higher activity than vancomycin. The present findings indicate that encapsulation of the selected phenolic compounds is favorable for improving their antibacterial profile, which could contribute to the endeavor for more efficient antibiotic therapy.

Cyclodextrins and their potential applications for delivering vitamins, iron, and iodine for improving micronutrient status.

Cyclodextrins (CDs) have been investigated as potential biopolymeric carriers that can form inclusion complexes with numerous bioactive ingredients. The inclusion of micronutrients (e.g. vitamins or minerals) into cyclodextrins can enhance their solubility and provide oxidative or thermal stability. It also enables the formulation of products with extended shelf-life. The designed delivery systems with CDs and their inclusion complexes including electrospun nanofibers, emulsions, liposomes, and hydrogels, show potential in enhancing the solubility and oxidative stability of micronutrients while enabling their controlled and sustained release in applications including food packaging, fortified foods and dietary supplements. Nano or micrometer-sized delivery systems capable of controlling burst release and permeation, or moderating skin hydration have been reported, which can facilitate the formulation of several personal and skin care products for topical or transdermal delivery of micronutrients. This review highlights recent developments in the application of CDs for the delivery of micronutrients, i.e. vitamins, iron, and iodine, which play key roles in the human body, emphasizing their existing and potential applications in the food, pharmaceuticals, and cosmeceuticals industries.

Silibinin solubilization: combined effect of co-solvency and inclusion complex formation

Objective Belonging to the class II drugs according to the biopharmaceutics classification system, silibinin (SLB) benefits from high permeability but suffers poor solubility that negatively affects the development of any delivery system. This research aimed to improve SLB solubility by combined use of co-solvency and complexation phenomena. Methods Solubility studies were performed using the phase solubility analysis according to the shake-flask method in the presence of ethanol and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) as a co-solvent and inclusion complexing agent, respectively. SLB release studies from chitosan nanoparticles were carried out in double-wall, diffusion cells using the optimized drug release medium. Results SLB solubility was mathematically optimized constraining to using the lowest concentrations of ethanol and HP-β-CD. SLB solubility increased linearly with the increase of HP-β-CD concentration. The solubility in PBS-ethanol mixtures followed a log-linear model. SLB solubility in the presence of the ethanol co-solvent and HP-β-CD complexing agent was optimized by adopting a genetic algorithm suggesting the phosphate buffer saline solution supplemented by 6%v/v ethanol and 8 mM HP-β-CD as an optimized medium. The optimized solution was examined to study SLB release from chitosan nanoparticles (4.5 ± 0.2% drug loading) at 37 °C under static conditions. The sigmoidal release profile of SLB from the particles indicated a combination of erosion and diffusion mechanisms governing drug release from the nanoparticles. Conclusion SLB solubility in a buffered solution supplemented by ethanol co-solvent and HP-β-CD complexing agent is a function of free drug present in the semi-aqueous media, the drug-ligand binary complex, and the drug/ligand/co-solvent ternary complex.

β-cyclodextrin inclusion complexes with short-chain phenolipids: An effective formulation for the dual sustained-release of phenolic compounds

The β-cyclodextrin and short-chain alkyl gallates (A-GAs), which are representative of phenolipids, such as butyl, propyl, ethyl, and methyl gallates, were chosen to form inclusion complexes by the use of the freeze-drying process. In the everted rat gut sac model, HPLC-UV analysis demonstrated that the released A-GAs from inclusion complexes were degraded to yield free gallic acid (GA) (sustained-release function 1). The small intestine membrane may be crossed by both the GA and the A-GAs. A-GAs may also undergo hydrolysis to provide GA (sustained-release function 2) following transmembrane transfer. Clearly, a helpful technique for the dual sustained-release of phenolic compounds is to produce β-cyclodextrin inclusion complexes with short-chain phenolipids. This will increase the bioactivities of phenolic compounds and prolong their in vivo residence length. Moreover, changing the carbon-chain length of these β-cyclodextrin inclusion complexes would readily modify the dual sustained-release behavior of the phenolic compounds. Thus, our work effectively established a theoretical foundation for the use of β-cyclodextrin inclusion complexes containing short-chain phenolipids as new source of functional food components to provide the body with phenolic compounds more efficiently.

Enhanced solubility and biological activities of Flufenamic acid through β-Cyclodextrin derivatives inclusion complexes: A comprehensive study

This study explores the formation of inclusion complexes between the solubility enhancement of Flufenamic acid (FNA) and various β-Cyclodextrins (β-CD, Hβ-CD, Mβ-CD, and Sβ-CD) using ultrasonic probe sonication method. The investigation encompasses a multi-faceted analysis, employing UV–Visible, FTIR, XRD, FE-SEM, TGA-DSC techniques and molecular docking studies. The UV–Visible spectra reveal absorption peak shifts and binding constants (Ka) indicate interaction strength, and thermodynamic parameters suggest spontaneous and favorable inclusion processes of β-CDs:FNA. Solid inclusion complexes of β-CDs:FNA were further characterized using FTIR, revealing alterations in functional groups indicative of complex formation. XRD analysis elucidates changes in crystallinity, while FE-SEM provides insights into morphological variations. Thermal stability is assessed through TGA-DSC, demonstrate the impact of inclusion on the complexes stability. Phase solubility diagrams illustrate the improved solubility of FNA in the presence of β-CDs. Mβ-CD:FNA exhibits the highest stability constant (1204 M−1), emphasizing its potential as an effective carrier. The binding energy of Mβ-CD:FNA (−46.72 kcal/mol) was lower than that of β-CD:FNA (−39.03 kcal/mol), Hβ-CD:FNA (−46.40 kcal/mol), and Sβ-CD:FNA (−46.29 kcal/mol), indicating that the hydroxypropyl group substitution enhanced the inclusion ability of β-CDs. Antibacterial activity studies against S. aureus and E. coli highlight enhanced efficacy of inclusion complexes with Mβ-CD:FNA (92.3 ± 0.18 % and 94.2 ± 0.17 %) demonstrating superior antibacterial activity. Cytotoxicity evaluations on HCT-116 cells reveal the safety profile of the β-CDs:FNA inclusion complexes, with Mβ-CD:FNA showing lower toxicity and high cell internalization compared to other formulations. The findings hold promise for applications in drug delivery, antimicrobial packaging, and the broader pharmaceutical and biotechnological fields.

Solid‐state room‐temperature phosphorescence activated by the end‐capping strategy of cyano groups

AbstractAvoiding the tedious process of crystal cultivation and directly obtaining organic crystals with desirable phosphorescent performance is of great significance for studying their structure and properties. Herein, a set of benzophenone‐cored phosphors with bright green afterglow are obtained on a large scale through in‐situ generation via an end‐capping strategy to suppress non‐radiative triplet excitons and reinforce the intermolecular interactions. The ordered arrangement of phosphors with alkyl‐cyano groups as regulators is crucial for the enhancement of room‐temperature phosphorescence (RTP) emission, which has been further verified by the attenuated lifetimes in isolated states through the formation of inclusion complexes upon binding with pillar[5]arenes. Moreover, the hierarchical interactions of phosphors, including hydrogen bonding, π‐π stacking interactions, and van der Waals forces, are quantified by crystal structures and theoretical calculation to deeply interpret the origins of RTP emission. With this study, we provide a potential strategy for the direct acquisition of crystalline organic phosphors and modulation of RTP.

Reversible Redox‐Driven Crystallization in a Paracyclophane Monolayer at a Solid–Liquid Interface

AbstractThe development and integration of cyclophanes into future functional materials require a detailed understanding of the physicochemical principles that underlie their properties, phase behavior, and in particular the relationship between structure and function. Here, electrochemically switchable crystallization of a ferrocene‐bearing 3D Janus tecton (M‐Fc) at the interface between highly oriented pyrolytic graphite (HOPG) and an electrolyte solution is demonstrated. The M‐Fc adlayer is successfully visualized under both ambient and electrochemical conditions using scanning tunneling microscopy. Voltammetric measurements show a surface‐confined redox process for the M‐Fc modified surface that drives the phase transition between a visible 2D ordered linear phase (M‐Fc0, with ferrocene in the neutral state) and an invisible gas‐like adsorption layer with high mobility when ferrocene is oxidized, M‐Fc+, and a “square scheme” mechanism explains the data. Analogous experiments in a ferrocene‐free tecton adlayer show no phase transition and confirm that the dynamics in M‐Fc are redox‐driven. On‐surface 3D nanoarchitectures are also demonstrated by forming inclusion complexes between M‐Fc and β‐cyclodextrin and device behavior through electrochemical scanning tunneling spectroscopy (STS). These results showcase the functional potential of this class of cyclophanes, which can find use in actuators, optical crystals, and other smart materials.

Exploring the formation mechanism of ferulic acid/hydroxypropyl-β-cyclodextrin inclusion complex: spectral analyses and computer simulation.

The biological functions of ferulic acid (FA) have garnered significant interest but its limited solubility and stability have led to low bioavailability. Hydroxypropyl-β-cyclodextrin (HP-β-CD), with its distinctive hollow structure, offers the potential for encapsulating hydrophobic molecules. The formation of an inclusion complex between FA and HP-β-CD may therefore be a viable approach to address the inherent limitations of FA. To investigate the underlying mechanism of the FA/HP-β-CD inclusion complex formation, a combination of spectral analyses and computer simulation was employed. The disappearance of the characteristic peaks of FA in Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) confirmed the formation of an inclusion complex between FA and HP-β-CD. Thermogravimetry-derivative thermogravimetry (TG-DTG) studies demonstrated that the thermal stability of FA was enhanced due to the encapsulation of FA within HP-β-CD. Molecular dynamics simulation also provided evidence that FA successfully penetrated the HP-β-CD cavity, primarily driven by van der Waals interactions. The formation of the complex resulted in more compact HP-β-CD structures. The bioavailability of FA was also strengthened through the formation of inclusion complexes with HP-β-CD. The findings of this study have contributed to a deeper understanding of the interactions between FA and HP-β-CD, potentially advancing a delivery system for FA and enhancing the bioavailability of insoluble active components. © 2024 Society of Chemical Industry.

Inclusion Complexes between β-Cyclodextrin and Gaseous Substances—N2O, CO2, HCN, NO2, SO2, CH4 and CH3CH2CH3: Role of the Host’s Cavity Hydration

The thermodynamic aspects of the process of inclusion complex formation between β-cyclodextrin (acting as a host) and gaseous substances (guests; N2O, CO2, NO2, SO2, HCN, CH4, CH3CH2CH3) are studied by employing well-calibrated and tested density functional theory (DFT) calculations. This study sheds new light on the intimate mechanism of the β-cyclodextrin/gas complex formation and answers several intriguing questions: how the polarity and size of the guest molecule influence the complexation thermodynamics; which process of encapsulation by the host macrocycle is more advantageous—insertion to the central cavity without hydration water displacement or guest binding accompanied by a displacement of water molecule(s); what the major factors governing the formation of the complex between β-cyclodextrin and gaseous substances are. The special role that the cluster of water molecules inside the host’s internal cavity plays in the encapsulation process is emphasized.

Enhanced Solubility of Ibuprofen by Complexation with β-Cyclodextrin and Citric Acid.

The ability of β-CD to form inclusion complexes with ibuprofen (IBU) and at the same time to make a two-phase system with citric acid was explored in the present study for achieving improved solubility and dissolution rate of IBU. Mechanical milling as well as mechanical milling combined with thermal annealing of the powder mixtures were applied as synthetic methods. Solubility and dissolution kinetics of the complexes were studied in compliance with European Pharmacopoeia (ICH Q4B). β-CD and citric acid (CA) molecules were shown to interact by both ball milling (BM), thermal annealing, as well as BM with subsequent annealing. Complexes were also formed by milling the three compounds (β-CD, CA and IBU) simultaneously, as well as by a consecutive first including IBU into β-CD and then binding the formed β-CD/IBU inclusion complex with CA. As a result, ternary β-CD/IBU/CA complex formed by initial incorporation of ibuprofen into β-CD, followed by successive formation of a two-phase mixture with CA, exhibited notably improved dissolution kinetics compared to the pure ibuprofen and slightly better compared to the binary β-CD/IBU system. Although the addition of CA to β-CD/IBU does not significantly increase the solubility rate of IBU, it must be considered that the amount of β-CD is significantly less in the ternary complex compared to the binary β-CD/IBU.

Energy Transfer-Based Recognition of Membrane Cholesterol by Controlling Intradistance of Linker.

Gold nanoparticles (AuNPs) are good candidates for donor material in energy transfer systems and can easily be functionalized with various ligands on the surface with Au-S bonding. Cyclodextrin (CD) forms inclusion complexes with fluorophores due to its unique structure for host-guest interaction. In this study, we fabricated βCD-functionalized AuNPs using different lengths of thiol ligands and recognized cholesterol to confirm the energy-transfer-based turn-on fluorescence mechanism. AuNP-βCD conjugated with various thiol ligands and quenched the fluorescein (Fl) dye, forming βCD-Fl inclusion complexes. As the distance between AuNPs and βCD decreased, the quenching efficiency became higher. The quenched fluorescence was recovered when the cholesterol replaced the Fl because of the stronger binding affinity of the cholesterol with βCD. The efficiency of cholesterol recognition was also affected by the energy transfer effect because the shorter βCD ligand had a higher fluorescence recovery. Furthermore, we fabricated a liposome with cholesterol embedded in the lipid bilayer membrane to mimic the cholesterol coexisting with lipids in human serum. These cellular cholesterols accelerated the replacement of the Fl molecules, resulting in a fluorescence recovery higher than that of pure lipid. These discoveries are expected to give guidance towards cholesterol sensors or energy-transfer-based biosensors using AuNPs.

Inclusion Complexes of Litsea cubeba (Lour.) Pers Essential Oil into β-Cyclodextrin: Preparation, Physicochemical Characterization, Cytotoxicity and Antifungal Activity.

The uses of natural compounds, such as essential oils (EOs), are limited due to their instability to light, oxygen and temperature, factors that affect their application. Therefore, improving stability becomes necessary. The objective of this study was to prepare inclusion complexes of Litsea cubeba essential oil (LCEO) with β-cyclodextrin (β-CD) using physical mixing (PM), kneading (KN) and co-precipitation (CP) methods and to evaluate the efficiency of the complexes and their physicochemical properties using ATR-FTIR, FT-Raman, DSC and TG. The study also assessed cytotoxicity against human colorectal and cervical cancer cells and antifungal activity against Aspergillus flavus and Fusarium verticillioides. The complexation efficiency results presented significant evidence of LCEO:β-CD inclusion complex formation, with KN (83%) and CP (73%) being the best methods used in this study. All tested LCEO:β-CD inclusion complexes exhibited toxicity to HT-29 cells. Although the cytotoxic effect was less pronounced in HeLa tumor cells, LCEO-KN was more active against Hela than non-tumor cells. LCEO-KN and LCEO-CP inclusion complexes were efficient against both toxigenic fungi, A. flavus and F. verticillioides. Therefore, the molecular inclusion of LCEO into β-CD was successful, as well as the preliminary biological results, evidencing that the β-CD inclusion process may be a viable alternative to facilitate and increase future applications of this EO as therapeutic medication, food additive and natural antifungal agent.

The contemplation of amylosefor the delivery of ulcerogenic nonsteroidal anti-inflammatory drugs.

This manuscript proposes an innovative approach to mitigate the gastrointestinal adversities linked withnonsteroidal anti-inflammatory drugs (NSAIDs) by exploiting amylose as a novel drug delivery carrier. The intrinsic attributes of V-amylose, such as its structural uniqueness, biocompatibility andbiodegradability, as well asits capacity to form inclusion complexes with diverse drug molecules, are meticulously explored. Through a comprehensive physicochemical analysis of V-amylose and ulcerogenic NSAIDs, the plausibility of amylose as a protective carrier for ulcerogenic NSAIDs to gastrointestinal regions is elucidated. This review further discusses the potential therapeutic advantages of amylose-based drug delivery systems in the management of gastric ulcers. By providing controlled release kinetics and enhanced bioavailability, these systems offer promising prospects for the development of more effective ulcer therapies.

Formation of Inclusion Complex of Curcumin and Tetrahydrocurcumin Prevents Angiogenesis by Inhibiting VEGF Activity: An in-Silico Study

Curcumin and tetrahydrocurcumin (THC) are known for their anticancer properties, but limited solubility in water hinders their effectiveness against cancer. In this study, we conducted an in silico exploration of β-cyclodextrin's potential to form inclusion complexes with curcumin or THC. The aim of this study was to assess the potential of curcumin and THC inclusion complexes to inhibit vascular endothelial growth factor (VEGF) signaling pathway, a key element in carcinogenesis. The in silico analysis involved multiple stages, such as bioactive compound preparation, biological activity prediction, 3D structure retrieval of VEGF and VEGFR, protein-ligand docking, and visualization. The results of the study demonstrated that both the curcumin- and THC-inclusion complexes exhibit a lower requirement for binding free energy to interact with VEGFR compared to curcumin or THC molecules alone. When VEGFR binds with curcumin, the curcumin-inclusion complex, or the THC-inclusion complex before interacting with VEGF, there is a notable increase in the binding free energy for the VEGF-VEGFR interaction. Specifically, the presence of THC-inclusion complex demonstrates the highest binding free energy for the VEGF-VEGFR interaction. The molecular dynamic simulation study shows that when VEGFR binds with curcumin, curcumin-inclusion complex, or THC-inclusion complex, the fluctuation of amino acid residues in VEGFR decreases compared to the VEGFR protein structure before binding with these molecules. In conclusion, this study suggests that the formation of inclusion complexes holds considerable promise for enhancing the anticancer potential of curcumin and THC by augmenting their anti-angiogenic activity.