Formation Of Inclusion Complexes Research Articles

Cyclodextrin microneedles for the delivery of a nanoparticle-based peptide antigen vaccine

In recent years, microneedles (MNs) have gained considerable interest in drug formulation due to their non-invasive and patient-friendly nature. Dissolving MNs have emerged as a promising approach to enhance drug delivery across the skin in a painless manner without generating sharp waste and providing the possibility for self-administration. Cyclodextrins, a group of cyclic oligosaccharides, are well-established in pharmaceutical products due to their safety and unique ability to form inclusion complexes with various drug molecules. In this manuscript, we report the development and characterization of dissolving MNs composed of cyclodextrins for intradermal delivery of a cyclodextrin-based nanoparticulate vaccine. Different cyclodextrins were tested and the most promising candidates were fabricated into MNs by micromolding. The MNs' piercing effectiveness and drug permeation across the skin were tested ex vivo. Furthermore, in vivo studies were carried out to assess the skin's tolerance to cyclodextrin-based MNs, and to evaluate the immune response using a model peptide antigen in a mouse model. The data revealed that the MNs were well-tolerated and effective, even leading to dose-sparing effects. This study highlights the potential of cyclodextrin-based dissolving MNs as a versatile platform for intradermal vaccine delivery, providing a compatible matrix for nanoparticulate formulations to enhance immune responses.

Moment Analysis Method for Measurement of Reaction Equilibrium and Rate Constants by Using High-Performance Liquid Chromatography.

The moment analysis method was developed for the determination of association equilibrium constant (KA) and association (ka) and dissociation (kd) rate constants of intermolecular interactions between solute and ligand molecules. They are accurately determined by using moment equations from elution peak profiles because they are measured by using high-performance liquid chromatography (HPLC) under preferable conditions that neither immobilization nor chemical modification (i.e., fluorescence labeling) of solute and ligand molecules is required. To demonstrate the effectiveness of the method, it was applied to the inclusion complex formation system between dibenzo-18-crown-6 (DB18C6) and alkaline earth metal cations, i.e., Mg2+, Ca2+, and Sr2+, as a concrete example. Because the diameter of the three metal cations is smaller than that of the inner cavity of DB18C6, the values of KA, ka, and kd were analytically determined by assuming the stoichiometry of 1:1 between DB18C6 and the metal cation. They reflected the influence of the difference in the size between the inner cavity of DB18C6 and the metal cations on the inclusion complex formation. It seems that the moment analysis method based on HPLC separation is effective for the multifaceted analysis of chemical reactions because some characteristics of the method are different from those of other conventional methods. It must contribute to the dissemination of an opportunity for the study of chemical reactions to many researchers because of the versatility of HPLC.

Preparation and Characterization of a Novel Salicin-Cyclodextrin Complex.

Bioactive compounds extracted from plants can provide wide health benefits. However, some molecules have limited applications as pharmaceuticals due to their limited solubility, poor bioavailability, and low stability when exposed to environmental factors. Their integration in formulations that can deliver them to physiological targets while preserving their biological activity can enhance their usage in improving human health. This research provides a delivery system design to enhance the solubility, stability and to mask the bitter taste of salicin. Thus, a novel salicin-β-cyclodextrin complex was prepared and analyzed by X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, FTIR, Raman and UV-Vis spectroscopy. The analytical and computational methods provided clear and distinct evidence for inclusion of salicin within the β-cyclodextrin cavity and brought important findings for the characterization of the inclusion complex. The present study showed that salicin and β-cyclodextrin can form inclusion complexes, both in solution and in solid state, and that the inclusion of salicin in the cavity of β-cyclodextrin leads to the improvement of its solubility and stability. Thus, the study communicates both qualitative and quantitative knowledge about the preparation of a new salicin-β-cyclodextrin inclusion complex suggesting its potential applications in pharmaceutical industry and medical sciences, as formulations with better compliance for the patient, with increased bioavailability, and easier control of dosage.

Curcumin/Carrier Coprecipitation by Supercritical Antisolvent Route.

In this work, polyvinylpyrrolidone (PVP)- and β-cyclodextrin (β-CD)-based composite powders containing curcumin (CURC) were obtained through the supercritical antisolvent (SAS) technique. Pressure, total concentration of CURC/carrier in dimethylsulfoxide, and CURC/carrier ratio effects on the morphology and size of the precipitated powders were investigated. Using PVP as the carrier, spherical particles with a mean diameter of 1.72 μm were obtained at 12.0 MPa, 20 mg/mL, and a CURC/PVP molar ratio equal to 1/2 mol/mol; using β-CD as the carrier, the optimal operating conditions were 9.0 MPa and 200 mg/mL; well-defined micrometric particles with mean diameters equal to 2.98 and 3.69 μm were obtained at molar ratios of 1/2 and 1/1 mol/mol, respectively. FT-IR spectra of CURC/ β-CD inclusion complexes and coprecipitated CURC/PVP powders revealed the presence of some peaks of the active compounds. The stoichiometry of the complexes evaluated through the Job method revealed that β-CD formed inclusion complexes with CURC at a molar ratio equal to 1/1. Dissolution profiles revealed that in comparison with the curve of the pure ingredient, the SAS-processed powders obtained using both PVP and β-CD have an improved release rate.

Quantifying the bitter masking effect of drug-cyclodextrin complexation: NMR-ROESY mixing time approach

Taste, especially unpleasant taste, can be key for patient compliance. In the formulation development process, drug-cyclodextrin (CD) inclusion complexes are often used to improve the solubility of a drug and/or mask its bitterness. This study aimed to evaluate the bitter masking effect of CDs on different drugs using NMR-ROESY analysis, human sensory tests, and e-tongue measurements. The strength of inclusion complex formation between drugs and CDs was investigated by NMR-ROSEY, and these results were compared to human sensory test results. In the sensory test, participants identified which drug-CD inclusion complexes were not bitter. NMR-ROSEY results aligned with the sensory tests; short magnetization transfer times corresponded to masked bitterness. The electrical tongue was not able to detect the taste of any of the drug-CD inclusion complexes. Additionally, we used NMR-ROSEY to determine which drug-CD inclusion complex formed in a system with multiple drug substances present. This research offers valuable insights into the bitter masking effect of CDs on different drugs and presents a comprehensive evaluation approach using various methods. This knowledge has significant implications for the pharmaceutical industry, clinical practice, and patient care, contributing to improved patient compliance and satisfaction with bitter medications.

Synthesis, characterization, molecular modeling, binding energies of β-cyclodextrin-inclusion complexes of quercetin: Modification of photo physical behavior upon β-CD complexation

We prepared a naturally occurring flavanoid namely quercetin from tea leaves and analyzed by Absorption, Emission, FT-IR, 1H, 13C nmr spectra and ESI-MS analysis. The inclusion behavior of quercetin in cyclodextrins like α-, β-, γ-, per-6-ABCD and mono-6-ABCD cavities were supported such as UV–vis., Emission, FT-IR and ICD spectra and energy minimization studies. From the absorption and emission results, the type of complexes formed were found to depend on stoichiometry of Host:Guest. FT-IR data of CD complexes of quercetin supported inclusion complex formation of the substrate with α-, β- and γ-CDs. The inclusion of host–guest complexation of quercetin with α-, β-, γ-CDs, per-6-ABCD and mono-6-ABCDs provides very valuable information about the CD:quercetin complexes, the study also shows that β-CD complexation improves water solubility, chemical stability and bioavailability of quercetin. Besides, phase solubility studies also supported the formation of 1:1 drug-CD soluble complexes. All these spectral results provide insight into the binding behavior of substrate into CD cavity in the order per-6-ABCD > Mono-6-ABCD > γ-CD > β-CD > α-CD. The proposed model also finds strong support from the fact with excess CD this exciton coupling disappears indicates the formation of only 1:1 complex.

Electrospinning for producing antifungal nanofibers consisting of prochloraz/hydroxypropyl-γ-cyclodextrin inclusion complex

Prochloraz is an extensively used imidazole fungicide in agriculture, but low water solubility limits its application. In the present study, inclusion complex nanofibers of prochloraz and Hydroxypropyl-γ-Cyclodextrin (prochloraz/HPγCD-IC-NF) were prepared by electrospinning method. The results of various characterization experiments indicated that prochloraz was effectively encapsulated in the cyclodextrin cavity to form inclusion complex nanofibers. Phase solubility study demonstrated that HPγCD had a significant solubilization effect on prochloraz. In 10 mM HPγCD solution, the solubility of prochloraz was increased about 2.68 times. Thermogravimetric analysis experiments indicated the beginning thermos-decomposed temperature of prochloraz in prochloraz/HPγCD-IC-NF was raised by 31℃ (from 281℃ to 312℃). The molecular simulation visually showed the best state and the most stable model of prochloraz entering the cyclodextrin cavity. In addition, the fungal inhibitory activity of prochloraz/HPγCD-IC-NF against Gibberella was 4.559 times to that of prochloraz. In conclusion, the preparation of inclusion nanofibers can improve the water solubility, thermal stability and antifungal activity of mimosine, which has the potential to reduce environmental damage in agricultural applications.

Application of Biomaterials in the Development of Hydrogel-Forming Microneedles Integrated with a Cyclodextrin Drug Reservoir for Improved Pharmacokinetic Profiles of Telmisartan.

Telmisartan (TEL) is a promising antihypertensive agent among other angiotensin receptor blockers. However, its oral application is limited by its poor water solubility. This study presents the successful utilization of biomaterial-based hydrogel-forming microneedles integrated with a direct compressed tablet reservoir (HFMN-DCT) for the transdermal delivery of telmisartan in the treatment of hypertension. The combination of PVP, PVA, and tartaric acid was used in the HFMN formulation. A range of cross-linking temperatures and times were employed to optimize the characteristics of the HFMN. The HFMN exhibited excellent swelling capacity, mechanical strength, and insertion properties. Additionally, the poorly soluble characteristic of TEL was improved by the inclusion complex formulation with β-cyclodextrin (βCD). Phase solubility analysis showed an Ap-type diagram, indicating a higher-order complex between TEL and βCD, with respect to βCD. A ratio of TEL:βCD of 1:4 mM demonstrates the highest solubility enhancement of TEL. The inclusion complex formation was confirmed by FTIR, XRD, DSC, and molecular docking studies. A significantly higher release of TEL (up to 20-fold) from the inclusion complex was observed in the in vitro release study. Subsequently, a DCT reservoir was developed using various concentrations of sodium starch glycolate. Essentially, both the HFMN and DCT reservoir exhibit hemocompatibility and did not induce any skin irritation. The optimized combination of the HFMN-DCT reservoir showed an ex vivo permeation profile of 83.275 ± 2.405%. Notably, the proposed system showed superior pharmacokinetic profiles in the in vivo investigation using male Wistar rats. Overall, this study highlights the potential of HFMN-DCT reservoir systems as a versatile platform for transdermal drug delivery applications.

Development of a gastroprotector from Algrizea minor essential oil complexed with β-Cyclodextrin

Algrizea minor, a member of the Myrtaceae family, is found in the Cerrado and Caatinga biomes. Essential oils (EO) are highly volatile, prompting the need to minimize volatilization losses and enhance their therapeutic effects. Cyclodextrins, cyclic and inert oligosaccharides, have the capability to form inclusion complexes with various molecules. Gastritis, an inflammatory condition, manifests painful episodes that may involve gastric and duodenal peptic ulcers. This study aims to evaluate the pharmacological potential of Algrizea minor essential oil in both free and complexed forms with β-Cyclodextrin (β-CD). The inclusion complex was created by combining essential oil and β-CD in a 1:1 ratio based on the molecular weight of the major compound in the oil. Characterization was conducted using Fourier-Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Thermogravimetry (TG). Gastroprotective capacity, physical barrier, and pathways of gastroprotection were assessed. The essential oil distinguished itself with the presence of β-Pinene and α-Pinene. Characterization of the inclusion complex revealed features of both the EO and β-CD. Tests demonstrated the curative efficacy of both free and complexed oils, with effectiveness dependent on the dosage. Intense gastroprotective activity was observed, with 90.25% and 99% inhibition of gastric injury for the free and complexed oils, respectively. It was determined that the pharmacological mechanism of action involves the stimulation of sulfhydryl compound production, the expression of nitric oxide (NO) and ATP-dependent potassium channels. Cytokines and oxidative stress were measured, and their responses contradicted the gastroprotection analysis. The tests highlighted the curative efficiency of both free and complexed oils, showing intensified gastroprotective activity when Algrizea minor essential oil was complexed with β-Cyclodextrin.

Inclusion complexes of β-cyclodextrin with isomeric ester aroma compounds: Preparation, characterization, mechanism study, and controlled release

Cyclodextrins (CDs) have been discovered to provide an efficient solution to the limited application of ester aroma molecules used in food, tobacco, and medication due to their strong smell and unstable storage. This work combined molecular modeling and experimental to analyze the conformation and controlled release of isomeric ester aroma compounds/β-CD inclusion complexes (ICs). The investigation revealed that ester aroma compounds could be effectively encapsulated within the β-CD cavity, forming ICs with low binding affinity. Furthermore, the key driving forces in ICs were identified as hydrogen bonds and van der Waals interactions through theoretical simulation. Results from the Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR) and Isothermal titration calorimetry (ITC) experiments confirmed the intermolecular interaction predicted by the molecular model. Notably, the release rate of aroma compounds from L-menthyl acetate/β-CD (LMA/β-CD) IC exceeded that of terpinyl acetate/β-CD (TA/β-CD) IC. This difference is attributed to the length of the chain of aroma molecules and the variation in the position of functional groups, influencing the stable formation of ICs with β-CD. These findings hold potential implications for refining the application of ICs across diverse industries.

Cyclodextrins: Establishing building blocks for AI-driven drug design by determining affinity constants in silico

Cyclodextrins (CDs) are cyclic carbohydrate polymers that hold significant promise for drug delivery and industrial applications. Their effectiveness depends on their ability to encapsulate target molecules with strong affinity and specificity, but quantifying affinities in these systems accurately is challenging for a variety of reasons. Computational methods represent an exceptional complement to in vitro assays because they can be employed for existing and hypothetical molecules, providing high resolution structures in addition to a mechanistic, dynamic, kinetic, and thermodynamic characterization. Here, we employ potential of mean force (PMF) calculations obtained from guided metadynamics simulations to characterize the 1:1 inclusion complexes between four different modified βCDs, with different type, number, and location of substitutions, and two sterol molecules (cholesterol and 7-ketocholesterol). Our methods, validated for reproducibility through four independent repeated simulations per system and different post processing techniques, offer new insights into the formation and stability of CD-sterol inclusion complexes. A systematic distinct orientation preference where the sterol tail projects from the CD's larger face and significant impacts of CD substitutions on binding are observed. Notably, sampling only the CD cavity's wide face during simulations yielded comparable binding energies to full-cavity sampling, but in less time and with reduced statistical uncertainty, suggesting a more efficient approach. Bridging computational methods with complex molecular interactions, our research enables predictive CD designs for diverse applications. Moreover, the high reproducibility, sensitivity, and cost-effectiveness of the studied methods pave the way for extensive studies of massive CD-ligand combinations, enabling AI algorithm training and automated molecular design.

Formulation Studies with Cyclodextrins for Novel Selenium NSAID Derivatives.

Commercial cyclodextrins (CDs) are commonly used to form inclusion complexes (ICs) with different molecules in order to enhance their water solubility, stability, and bioavailability. Nowadays, there is strong, convincing evidence of the anticancer effect of selenium (Se)-containing compounds. However, pharmaceutical limitations, such as an unpleasant taste or poor aqueous solubility, impede their further evaluation and clinical use. In this work, we study the enhancement of solubility with CD complexes for a set of different nonsteroidal anti-inflammatory drug (NSAID) derivatives with Se as selenoester or diacyl diselenide chemical forms, with demonstrated antitumoral activity. The CD complexes were analyzed via nuclear magnetic resonance (NMR) spectroscopic techniques. In order to obtain additional data that could help explain the experimental results obtained, 3D models of the theoretical CD-compound complexes were constructed using molecular modeling techniques. Among all the compounds, I.3e and II.5 showed a remarkable increase in their water solubility, which could be ascribed to the formation of the most stable interactions with the CDs used, in agreement with the in silico studies performed. Thus, the preliminary results obtained in this work led us to confirm the selection of β and γ-CD as the most suitable for overcoming the pharmaceutical drawbacks of these Se derivatives.

Optimization of β-cyclodextrin based ultrasonic-assisted extraction of apigenin and luteolin from celery seed using support vector regression and different nature-inspired optimization algorithms

This study aimed to extract apigenin and luteolin from celery seeds using 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) based ultrasonic-assisted technique. Optimal extraction conditions were determined through the integration of support vector regression combined with various optimization algorithms, including Genetic Algorithm, Particle Swarm Optimization, Gray Wolf Optimizer, Bat Algorithm, Firefly Algorithm, and Cuckoo Search Algorithm. The identified optimal conditions included an extraction time of 52 min, an HP-β-CD concentration of 24 mg/mL, and a solvent-to-solid ratio of 24 mL/g. Under these conditions, the predicted apigenin and luteolin content in the extract were 0.156 and 0.814 mg/g, respectively, closely aligning with the actual values of 0.158 ± 0.005 mg/g and 0.807 ± 0.008 mg/g. Notably, the HP-β-CD/water extract exhibited significantly higher concentrations of active ingredients and antioxidant activity compared to the water extract, with the content of apigenin and luteolin in the water extract being only 25 and 45%, respectively, compared to the HP-β-CD/water extract. Regarding the antioxidant effect, the water extract displayed a 50% scavenging capacity (SC50) of 331.29 ± 20.5 g/mL, whereas the SC50 for the HP-β-CD/water extract was 89.04 ± 4.70 g/mL. Molecular modeling and IR spectra analysis also suggested the formation of inclusion complexes between HP-β-CD and apigenin/luteolin. These findings suggested that HP-β-CD could be a preferable alternative to conventional solvents due to its advantages, such as easier control, safety, and cost-effectiveness. In addition, the use of support vector regression and nature-inspired optimization algorithms could be promising alternatives to traditional response surface methodology.

Stable nanometer-size beta-cyclodextrin – CeO2-x colloidal nanoparticles with high free radical scavenging activity

Cyclodextrin (CD) molecules are well-known for their ability to form inclusion complexes with hydrophobic molecules, including small drug molecules and lipophilic antioxidants. The combination of nanoparticles (NPs) with antioxidant properties (so-called nanozymes) and hydrophobic antioxidant molecules using CD@NP complexes can increase sufficiently the antioxidant efficiency of both components due to synergistic effect. Here we propose the new method of obtaining β-CD@CeO2-x complexes with addition of β-CD on the stage of syntheses of NPs. As a result, highly stable colloidal solutions of nanometer-size (2–3 nm) β-CD@CeO2-x nanoparticles were obtained. The stabilization effect of β-CD molecules was shown. Obtained β-CD@CeO2-x complexes reveal high antiradical activity in the number of experiments (including •OH and O2– scavenging) related to Ce3+/Ce4+ redox switching in nanoceria. The aggregation behavior of β-CD@CeO2-x complexes in various biological media was studied and the ways to improve their stability were proposed.

The recent development of β‐cyclodextrin‐based catalysts system in click reactions: A review

A significant challenge for scientists today is to design green and eco‐friendly catalysts based on green chemistry with high catalytic performance and recycling properties. Many studies have aimed to address environmental issues by developing green chemical processes and catalysts that reduce the production of harmful substances. β‐Cyclodextrin (β‐CD), a class of cyclic oligomers, has garnered considerable attention in recent decades. It has been utilized as a green alternative catalyst in various organic conversions, demonstrating satisfactory catalytic activity and improved efficiency of organic reactions. The availability, non‐toxicity, low cost, renewability, and high performance in organic transformations are several benefits of cyclodextrins that have attracted interest from research groups worldwide. The click reaction is well‐known in green chemistry for its high selectivity and efficiency in producing 1,2,3‐triazoles with significant medicinal activities. This reaction involves aryl/alkyl halides, alkynes, and NaN3 under ambient conditions to generate necessary scaffolds called 1,2,3‐triazoles. Therefore, finding green approaches for synthesizing 1,2,3‐triazoles is of great interest. In recent decades, significant advancements have been made in developing metal‐catalyzed click reactions to synthesize 1,2,3‐triazole derivatives. Carolyn Bertozzi, Morten Meldal, and Barry Sharpless were awarded the Nobel Prize in Chemistry in 2022 for their contributions to the foundations of click and bio‐orthogonal chemistry. In transition, metal‐catalyzed click reactions, using modified β‐CD derivatives as catalysts is particularly advantageous because of their valuable catalytic properties and their ability to form inclusion complexes with different metals. This review focuses on the catalyzed click reaction using β‐CD‐based catalysts to prepare triazoles. Using biodegradable β‐CD has made the method safe, sustainable, and eco‐friendly. The click reaction has provided access to various 1,2,3‐triazoles essential in pharmaceutical products and exhibits diverse biological activities. The specific purpose of this review is to summarize the application of β‐CD‐based catalyst systems in click reactions.

Enhancing solubility and stability of piperine using β-cyclodextrin derivatives: computational and experimental investigations

Piperine (PP), a natural alkaloid found in black pepper, possesses significant bioactivities. However, its use in pharmaceutical applications is hindered by low water solubility and susceptibility to UV light degradation. To overcome these challenges, we investigated the potential of β-cyclodextrin (βCD) and its derivatives with dimethyl (DMβCD), hydroxy-propyl (HPβCD) and sulfobutyl-ether (SBEβCD) substitutions to enhance the solubility and stability of PP. This study employed computational and experimental approaches to examine the complexation between PP and βCDs. The results revealed the formation of two types of inclusion complexes: the P-form and M-form involving the insertion of piperidine moiety and the methylene-di-oxy-phenyl moiety, respectively. These complexes primarily rely on van der Waals interactions. Among the three derivatives, the PP/SBEβCD complex exhibited the highest stability followed by HPβCD, as attributed to maximum atom contacts and minimal solvent accessibility. Solubility studies confirmed the formation of inclusion complexes in a 1:1 ratio. Notably, the stability constant of the inclusion complex was approximately two-fold higher with SBEβCD and HPβCD compared to βCD. The DSC thermograms provided confirmation of the formation of the inclusion complex between the host and guest. These findings highlight the potential of βCD derivatives to effectively encapsulate PP, improving its solubility and presenting new opportunities for its pharmaceutical applications. Communicated by Ramaswamy H. Sarma

Substantial solubility and fluorescence property changes upon inclusion of rutaecarpine in cucurbit[7]uril: Kinetics and thermodynamics of binding

The effect of acid and cucurbit[7]uril (CB7) additions on the solubility and fluorescent properties of rutaecarpine (Rut), a pharmaceutically important plant alkaloid, was studied in aqueous solution. Approximately 550-fold water-solubility enhancement was achieved upon inclusion complex formation with CB7. The cationic protonated alkaloid (RutH+) was encapsulated in CB7 with a binding constant more than three orders of magnitude larger than that of the uncharged Rut. The stabilization of RutH+ by the host macrocycle led to a pKa increase of ∼3.3 units compared with that found in water. The substantial increase in fluorescence quantum yield upon RutH+–CB7 production could be exploited for the sensitive visualization of pH differences in the range of 4.5–6.5. The highly exothermic complexation was accompanied by considerable entropy diminution, partly because of the critical role of hydrogen bonding between the constituents. The rate constants of the creation and dissociation of RutH+–CB7 were 2.5 × 106 M−1 s−1 and 0.94 s−1 at 283 K, respectively.

Contrasting caging effect on the photodynamics of 1′-hydroxy-2′-acetonaphthone

Confined environments, such as cyclodextrins, offer a convenient method to modulate the excited-state (ES) photodynamics of a probe molecule, and studies on such topics have attracted tremendous attention in numerous biological and chemical fields. Current study explores the photodynamic modulations of an ESIPT probe, 1′-hydroxy-2′-acetonaphthone (1HAN), by two homologous cyclodextrin derivatives having different cavity sizes, namely hydroxypropyl-β-cyclodextrin (HPβCD) and hydroxypropyl-γ-cyclodextrin (HPγCD), using multispectroscopic techniques. 1HAN shows substantial fluorescence enhancement after forming 1:1 inclusion complexes with both of these host molecules. Time-resolved (TR) anisotropy studies indicate substantially longer rotational relaxation times for the 1HAN-HP(β/γ)CD systems compared to the free 1HAN, further supporting the formation of inclusion complexes in the current systems. Intriguingly, TR fluorescence studies reveal contrasting modulation of the ES equilibrium between keto (K1*) and twisted keto (K2*) tautomers of 1HAN by HPβCD and HPγCD hosts, respectively. In the presence of the HPβCD host, the ES equilibrium between keto tautomers of 1HAN is shifted more towards the K1* form. On the contrary, the ES equilibrium shifts more towards the K2* form of the dye in the presence of the HPγCD host. This contrasting modulation in the ES equilibrium between K1* and K2* tautomers of 1HAN indicates that the dimension of the interior cavity of the host and hydrophobic interactions play a decisive role in regulating the photodynamics of the excited 1HAN dye.

Molecular insights into the formation of drug-polymer inclusion complex

Drug-polymer inclusion complex (IC) has been viewed as a novel solid form of drugs for property modification. Nonetheless, our understanding of the formation mechanism remains limited. This work aims to provide insight into the molecular processes governing the structural construction of carbamazepine (CBZ) and griseofulvin (GSF) channel-type ICs in the presence of guest polymers. Leveraging microdroplet melt crystallization, we successfully unveiled the single-crystal structures of these ICs, enabling structural analysis, density functional theory calculations, and molecular dynamics simulations. The results collectively elucidate the disparity between CBZ and GSF channels in terms of their autonomy in the absence of guest polymers. CBZ molecules can spontaneously assemble into stable channel structures independently, capitalizing on their unique mortise-tenon architecture and robust π…π interactions. Conversely, GSF channels lack sufficient support from weak Cl…O and C-H…π intermolecular interactions and necessitate the insertion of guest molecules to stabilize their structures. We further calculated the eleven structurally determined drug-polymer ICs and found that their channel sizes consistently fall within a narrow range of 3.81–5.18 Å although they adopt diverse approaches to construct channel structures. We anticipate that these findings will inspire continued exploration of this novel solid form, facilitating theoretical predictions and practical applications in pharmaceutical development.

Enhanced stability of natural vitamin E from palm oil by forming inclusion complexes with cyclodextrin and its application on PLA fabric

Vitamin E extracted from palm oil and palm fatty acid distillate, through biodiesel conversion, was stabilized by forming inclusion complexes with β-CD and HP-β-CD. These complexes were successfully applied to nonwoven PLA fabrics.