Cyclodextrin Research Articles

Designing and preparing supramolecular encapsulation systems based on fraxetin and cyclodextrins for highly selective detection of nicotine

Herein, a series of water-soluble supramolecular inclusion complexes (ICs) probes were prepared using cyclodextrins (CDs) and fraxetin (FRA) to detect nicotine (NT) with high selectivity in vitro and in vivo. The FRA/CD ICs prepared through the saturated solution method exhibited excellent water solubility, stability, and biocompatibility. A clear host-guest inclusion model was provided by the theoretical calculations. The investigation revealed that NT was able to enter into the cavities of FRA/β-CD IC and FRA/γ-CD IC, and further formed charge transfer complexes with FRA in the CD cavities, resulting in a rapid and highly selective fluorescence-enhanced response with the lowest detection limits of 1.9 × 10−6 M and 9.7 × 10−7 M, and the linear response ranged from 0.02 to 0.3 mM and 0.01–0.05 mM, respectively. The IC probes showed good anti-interference performance to common interferents or different pH environments, with satisfactory reproducibility and repeatability of response to NT. Furthermore, the potentiality of the probes was confirmed through fluorescence imaging experiments using human lung cancer cells and the lung tissue of mice. This study offers a fresh perspective for detecting NT in environmental and biomedical analysis.

Anti‐Inflammatory Nanotherapies Based on Bioactive Cyclodextrin Materials

Despite remarkable advances in understanding the mechanisms underlying inflammation, the currently available anti‐inflammatory therapies have many limitations, such as poor efficacies, low selectivity, and severe adverse effects. Bioactive materials with intrinsically anti‐inflammatory activities have emerged as promising drug candidates for the treatment of inflammatory disorders. Among them, nanotherapies based on bioactive cyclodextrin (CD) materials have attracted much attention, owing to their multiple advantages, including broad availability, well‐controlled structures, easy functionalization, good processibility, high cost‐effectiveness, and excellent biocompatibility. This review provides a comprehensive overview of the recent advancements in the development and applications of anti‐inflammatory nanoparticles (NPs) based on bioactive CD materials, with special focus on reactive oxygen species‐scavenging NPs and NPs capable of regulating inflammatory cell recruitment and activation. In addition, the applications of these anti‐inflammatory nanotherapies in the treatment of different acute/chronic inflammatory diseases are highlighted. Furthermore, major challenges in the clinical translation of these new generation anti‐inflammatory therapies derived from bioactive CD materials are discussed.

A DFT-Based Mechanism Analysis of the Cyclodextrin Inclusion on the Radical Scavenging Activity of Apigenin.

Natural flavonoids are renowned for their exceptional antioxidant properties, but their limited water solubility hampers their bioavailability. One approach to enhancing their water solubility and antioxidant activity involves the use of cyclodextrin (CD) inclusion. This study investigated the impact of CD inclusion on the three primary radical scavenging mechanisms associated with flavonoid antioxidant activity, utilizing apigenin as a representative flavonoid and employing density functional theory (DFT) calculations. Initially, the optimized geometries of CD-apigenin inclusion complexes were analyzed, revealing the formation of hydrogen bonds between CD and apigenin. In less polar environments, the inclusion complex strengthened the bond dissociation enthalpies of hydroxyl groups, thereby reducing antioxidant activity. Conversely, in polar environments, the inclusion complex had the opposite effect by lowering proton affinity. These findings align with experimental results demonstrating that CD inclusion complexation enhances flavonoid antioxidant activity in aqueous ethanol solutions.

Transcriptomics and Physiological Analyses Reveal Changes in Paclitaxel Production and Physiological Properties in Taxus cuspidata Suspension Cells in Response to Elicitors.

In this research, the cell growth, physiological, and biochemical reactions, as well as the paclitaxel production, of Taxus cuspidata suspension cells after treatment with polyethylene glycol (PEG), cyclodextrin (CD), or salicylic acid (SA) (alone or in combination) were investigated. To reveal the paclitaxel synthesis mechanism of T. cuspidata suspension cells under elicitor treatment, the transcriptomics of the Control group and P + C + S group (PEG + CD + SA) were compared. The results show that there were no significant differences in cell biomass after 5 days of elicitor treatments. However, the content of hydrogen peroxide (H2O2) and malondialdehyde (MDA), and the activities of phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO) after elicitor combination treatments were decreased compared with the single-elicitor treatment. Meanwhile, the antioxidant enzyme activity (superoxide dismutase (SOD), catalase (CAT), and peroxidase (PO)) and the contents of soluble sugar and soluble protein were increased after combination elicitor treatments. Additionally, the paclitaxel yield after treatment with the combination of all three elicitors (P + C + S) was 6.02 times higher than that of the Control group, thus indicating that the combination elicitor treatments had a significant effect on paclitaxel production in T. cuspidata cell suspension culture. Transcriptomics analysis revealed 13,623 differentially expressed genes (DEGs) between the Control and P + C + S treatment groups. Both GO and KEGG analyses showed that the DEGs mainly affected metabolic processes. DEGs associated with antioxidant enzymes, paclitaxel biosynthesis enzymes, and transcription factors were identified. It can be hypothesized that the oxidative stress of suspension cells occurred with elicitor stimulation, thereby leading to a defense response and an up-regulation of the gene expression associated with antioxidant enzymes, paclitaxel synthesis enzymes, and paclitaxel synthesis transcription factors; this ultimately increased the production of paclitaxel.

Supramolecular photoresponsive polyurethane with movable crosslinks based on photoisomerization of azobenzene

AbstractLight‐driven actuators are widely used for smart devices such as soft robots. One of the main challenges for actuators is achieving rapid responsiveness, in addition to ensuring favorable mechanical properties. Herein, we focused on photoresponsive polyurethane (CD‐Azo‐PU) based on controlling the crystallization of the hard segments in polyurethane (PU) by complexation between azobenzene (Azo) and cyclodextrins (CDs). CD‐Azo‐PU incorporated polyurethane as the main chain and a 1:2 inclusion complex between Azo and γCD as a movable crosslink point. Upon ultraviolet light (UV, λ = 365 nm) irradiation, the photoresponsiveness of CD‐Azo‐PU bent toward the light source (defined as positive), while that of the linear Azo polyurethane (Azo‐LPU) without peracetylated γ‐cyclodextrin diol (TAcγCD‐diOH) as a movable crosslinker bent in the direction opposite the light source. The bending rates were determined to be 0.25°/s for CD‐Azo‐PU and 0.083°/s for Azo‐LPU, indicating that the bending rate for CD‐Azo‐PU was faster than that for Azo‐LPU. By incorporating movable crosslinks into CD‐Azo‐PU, we successfully achieved specific photoresponsive actuation with an enhanced rate.

Quality by design-guided development of a capillary electrophoresis method for the simultaneous chiral purity determination and impurity profiling of tamsulosin.

Analytical Quality by Design principles using the design of experiments were applied for the development of a capillary electrophoresis method for the determination of enantiomeric purity and chemically related impurities of tamsulosin. From initial scouting experiments, a dual cyclodextrin (CD) system composed of sulfated β-CD and carboxymethyl-α-CD was selected as the chiral selector. A fractional factorial resolution V+ design was used for the identification of the critical process parameters, while a face-centered central composite design and Monte Carlo simulations were employed for final optimization and defining the design space of the method. The experimental conditions of the working point were: 30mM sodium phosphate buffer, pH 3.0, containing 40mg/mL sulfated β-CD and 7mg/mL carboxymethyl-α-CD, capillary temperature 18°C, applied voltage -23kV. Following the assessment of robustness by applying a Plackett-Burman design, the method was validated according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use guideline Q2(R1). The method allowed the quantification of the chiral impurity and three other related impurities at the 0.1 % level with acceptable accuracy and precision.

Clinical safety of remdesivir therapy in COVID-19 patients with renal insufficiency

Though remdesivir benefits COVID-19 patients, its use in those with renal dysfunction is currently limited due to concerns about possible toxic effects of accumulated sulfobutylether-β-cyclodextrin (SBECD) on liver and kidney. We examined renal and hepatic function for a month in renally-impaired COVID-19 patients who were treated or not treated with remdesivir to assess the safety of the drug. A retrospective study was performed in adult COVID-19 patients with glomerular filtration rates of <30 ml/min/1.73 m2 at admission to a tertiary care hospital between November 2020 and March 2022. Data on serum creatinine and liver chemistry were collected serially. A total of 101 patients with impaired renal function were analyzed, comprising 64 remdesivir-treated patients and 37 who did not receive any antiviral agent. Although remdesivir-treated patients were more likely to be infected with the Omicron variant (79.7% vs. 48.6%), baseline characteristics did not differ significantly between the two groups. Among patients who initially did not require dialysis, 18.4% (7/38) of remdesivir-treated patients developed acute kidney injury (AKI) at days 4–6, compared with 51.7% (15/29) of non-remdesivir-treated patients. Liver injury severity worsened in 3.1% (2/64) of remdesivir-treated patients and 5.4% (2/37) of non-remdesivir-treated patients at days 4–6. In addition, there was no significant increase in AKI and liver injury over time in remdesivir-treated patients, and there were no cases of discontinuation of remdesivir due to adverse reactions. Concerns regarding the safety of SBECD should not lead to hasty withholding of remdesivir treatment in renally-impaired COVID-19 patients.

Active and Intelligent Packaging: A Review of the Possible Application of Cyclodextrins in Food Storage and Safety Indicators.

Natural cyclodextrins (CDs) can be formed by 6, 7, or 8 glucose molecules (α-, β-, and γ-, respectively) linked in a ring, creating a cone shape. Its interior has an affinity for hydrophobic molecules, while the exterior is hydrophilic and can interact with water molecules. This feature has been used to develop active packaging applied to food, interacting with the product or its environment to improve one or more aspects of its quality or safety. It also provides monitoring information when food is optimal for consumption, as intelligent packaging is essential for the consumer and the merchant. Therefore, this review will focus on discerning which packaging is most appropriate for each situation, solubility and toxicological considerations, characterization techniques, effect on the guest properties, and other aspects related to forming the inclusion complex with bioactive molecules applied to packaging.

The protective effect of cyclodextrin on the color quality and stability of Cabernet Sauvignon red wine

The impact of cyclodextrins (CDs) on wine quality and stability remains largely unknown. This study systematically assessed the protective effect of the post-fermentation addition of CDs on color stability of red wine from the viewpoints of color characteristics, copigmentation and phenolic profiles. The grey relational analysis (GRA) and principal component analysis (PCA) methods were employed to dissect the key effective determinants related to color quality. The addition of CDs induced a significant hyperchromic effect of 8.19–25.40%, a significant bathochromic effect and an enhancement of the color intensity. Furthermore, the evolution of anthocyanin forms and the content of monomeric anthocyanins revealed that β-CD is a superior favorable cofactor during wine aging, but for long-term aging, 2-HP-β-CD and 2-HP-γ-CD are more beneficial in promoting the formation of polymerized anthocyanins and color stability. This work provides an important reference for the use of CDs to enhance the color quality and stability of red wines.

Sulfo-butyl ether β-cyclodextrin inclusion complexes of bosutinib: in silico, in vitro and in vivo evaluation in attenuating the fast-fed variability.

Bosutinib (BOS) is a BCS class IV drug that shows low oral bioavailability and high fast-fed variability. Various pharmaceutical formulations have been explored thus far in order to improve its bioavailability while avoiding fast-fed variability. In the present study, we explored cyclodextrin (CD) complexation strategy to overcome the aforementioned disadvantages associated with BOS. CD complexation is a simple, versatile and economic approach that enables formation of inclusion complexes, thereby improving aqueous solubility while nullifying pH-dependent solubility and fast-fed variability for poorly soluble drugs. Initially, we performed molecular dynamics and docking studies to select appropriate CD derivative. The results of in silico studies revealed that sulfo-butyl ether β-cyclodextrin (SBE-CD) offered superior binding affinity with BOS. Further, Job's plot revealed that 1:1 stoichiometry of BOS and CD resulted in enhancement of BOS solubility up to ~ 132.6-folds. In vitro release studies in bio-relevant media (fasted and fed state simulated gastric and intestinal fluids) revealed higher drug release while overcoming its pH-dependent solubility. In vitro studies on K562 cells demonstrated a 1.83-fold enhancement in cytotoxicity due to enhanced ROS production and G2/M phase arrest.In vivo pharmacokinetic studies in Sprague-Dawley rats revealed insignificant fast-fed variability with AUCfast/fed 0.9493 and Cmaxfast/fed 0.8291 being closer to 1 in comparison with BOS. Hence, we conclude that SBE-CD complexation could be a promising approach in diminishing fast-fed variability of BOS.

Preparation and Application of Polyrotaxane Cross-Linking Agent Based on Cyclodextrin in Gel Materials Field.

The cross-linking point of a conventional chemical cross-linking agent is fixed. Therefore, gels that are prepared with a conventional cross-linking agent have poor deformability, strength, shear resistance, and further properties. Some researchers have prepared a new cross-linking agent using cyclodextrin (CD). In a polyrotaxane cross-linking agent, the cross-linking points can slide freely along the molecule chain. The special "slide ring" structure can provide better elongation, strength, and other properties to gels, which can effectively expand the application of the gel's materials. This paper summarizes the preparation methods and applications from different types of CD and compares the improvements of properties (swelling, viscoelastic properties, etc.). In addition, the current results of our group are presented, and some ideas are provided for the development of polyrotaxane cross-linking agents.

SOLID DISPERSION SYSTEMS OF POORLY WATER SOLUBLE DRUG FEBUXOSTAT: PREPARATION, CHARACTERIZATION AND OPTIMIZATION

Febuxostat is a poor soluble drug used in the management of hyperuricemia and gout. The present study aims at increasing the solubility of febuxostat by solid dispersion technique with the aid of various polymers (Beta cyclodextrin, Soluplus®, HPMC E5, and Kolliphor® P 407) in various drug: carrier ratios employing the solvent evaporation method. Solid dispersions were evaluated for physical appearance, percentage yield, drug content, saturation solubility and dissolution properties. Saturation solubility data of the study depict an increased solubility of the solid dispersion compared to the pure drug. In in vitro release profiles revealed that formulation SD20, having drug: Kolliphor® P 407 in 1:9 ratio exhibited highest dissolution rate. The powder X-ray diffraction study and scanning electron microscopy (SEM) exhibited a crystalline to an amorphous transformation in the solid dispersion. The study demonstrated that solid dispersions are a highly effective technique to increase solubility and bioavailability of febuxostat.

Hypericin supramolecular assembles: A way to increase the skin availability and photodynamic efficiency in tumor cells

Cyclodextrins (CDs) are molecules approved by the FDA and show promise in increasing the solubility of hydrophobic molecules and making them more available to the skin. These CDs have been used to form complexes with some photosensitizers for Photodynamic Therapy (PDT), such as Hypericin (HY). HY is a lipophilic photosensitizer known for its exceptional fluorescence and singlet oxygen quantum yield generation of over 20 % under 590 nm irradiation. In this study, we found a six-fold increase in the release of HY in vitro after complexation with β-CD. The β-CDHY assembly also demonstrated better skin retention, which is crucial for the topical application of this photosensitizer. Furthermore, the β-CD complexation led to a significant increase in the phototoxicity of HY at three different light doses (3, 6, and 10 J cm−2) due to its improved water solubility and higher in vitro accumulation (approximately two times compared with free HY) in HeLa and Vero cell lines.

Recent advances in β‐cyclodextrin‐based catalysts for reducing toxic nitroaromatic: An overview

Regarding the incremental shortage of water resources, wastewater treatment is essential for guarding the ecosystem and the sufficient usage of water resources. Freshwater, a vital item of life for humans and animals, is in danger because of the existence of destructive pollutants, such as p‐nitrophenol (p‐NP), and organic azo dyes, leading to water pollution. Among environmental pollution, water pollution has been recognized as one of the important threat agents in charge of many illnesses in humans. Nitrophenols contain high stability and solubility in water, which causes health risks. It is essential to change these harmful chemicals into healthy materials to have a safe life on the globe. Nitro compounds obtained from industrial wastewater are a severe threat to human being health and living organisms. Hence, designing green strategies and environment‐friendly catalysts to reduce toxic contaminants such as nitro compounds and dyes is a considerable challenge. One technique to overcome this crisis is the catalytic hydrogenation of nitro compounds to the amines, which are invaluable and non‐toxic materials. Reducing nitroarenes can be synthesized the amines, vital intermediates in organic and biological chemistry. Designing green strategies in nitro reduction processes for synthetic organic chemists is a great challenge. The nitroarene reduction reaction is a very efficient, reliable, and environmentally friendly method for synthesizing amines. Cyclodextrin (CD) can be applied as an effective catalyst in many aqueous organic reactions. Their derivatives have exhibited outstanding performance in water‐mediated organic synthesis and are now of ongoing attraction to many scientists in various fields. CDs show better catalytic activity and selectivity due to their particular geometry and structural interactions. CDs catalyzed reactions have been getting significant attention recently due to their low toxicity, biodegradability, economically and eco‐friendly behavior. Many reports are available in the literature on CDs material considered promising catalysts in reducing nitro compounds. This review article focuses on the use of β‐CD catalyst systems as valuable catalysts in the hydrogenation of nitroarenes and overviews articles up to 2023.

Ternary cyclodextrin systems of terbinafine hydrochloride inclusion complexes: Solventless preparation, solid-state, and in vitro characterization

Cyclodextrins (CD) are used extensively in the pharmaceutical industry to improve the water solubility and bioavailability of drugs. Preparing ternary systems by applying a third component can enhance these beneficial effects. The complexation methods of these ternary systems are the same as those of two-component complexes. These methods are solvent (co-evaporation, co-precipitation, etc.) or solventless “green” techniques (co-grinding, microwave irradiation, etc.). Using solvent-free methods is considered to be an economically and environmentally desirable technology.This study aimed to prepare ternary systems by the co-grinding method and evaluate the effect of a third component by comparing it to products obtained by solvent methods, binary systems, and marketed products. For that, we used terbinafine hydrochloride as a model drug, sulfobutyl-ether-beta-cyclodextrin as a complexation agent and 5 or 15 w/w% of polyvinylpyrrolidone K-90 (PVP) or hydroxypropyl methylcellulose (HPMC) as auxiliary components.Physicochemical evaluation (X-Ray Diffractometry, Differential Scanning Calorimetry, Thermogravimetry) showed that new solid phases were formed, while Scanning Electron Microscopy was performed to study morphological aspects of the products. Fourier transform infrared spectroscopic measurements suggested different intermolecular interactions depending on the type of polymer. In vitro dissolution studies showed beneficial effects of CD and further improvement with the applied polymers. Products showed less cell toxicity with one exception.Both polymers enhanced the physicochemical and in vitro properties, suggesting a greater bioavailability of the model drug. However, the percentage of polymers applied did not appear to be an influencing factor for these properties.

Sustainable β- and γ-cyclodextrins for development of highly permeable thin film composite nanofiltration membranes

The use of macromolecules, such as cyclodextrins (CDs), given their porosity and compatibility with organic materials, are very attractive for the progress of polymeric membranes in nanofiltration (NF) of aqueous dye solutions. Two types of membranes were fabricated. Firstly, β- and γ-CDs were incorporated to polyamide (PA) thin film composite (TFC) membranes. These membranes, named CD/MPD-TMC, were prepared by conventional interfacial polymerization —i.e., an aqueous solution of m-phenylenediamine (MPD) followed by a solution of trimesoyl chloride (TMC) in hexane— by replacing a certain amount of the MPD monomer with varying proportions of CDs. Secondly, two-step double-IP (TD-IP) membranes were fabricated as follows: CDs were deposited atop the polymer support, followed by addition of TMC —forming a polyester (PE) layer—, and subsequently the membrane surface was modified with MPD molecules. In both CD/MPD-TMC and TD-IP membranes, the presence of CDs improved the membrane performance, the latter configuration leading to much higher water permeances. The TD-IP membrane using β-CD achieved the highest water permeance of 10 L m−2 h−1·bar−1 (LMH bar−1) and a rejection of acridine orange dye (265 Da) greater than 98 %. This represents a 6-fold increase in water permeance compared to bare PA (1.6 LMH bar−1). The enhanced water transport was mainly attributed to the more hydrophilic nature of the membranes and the presence of a PE layer with a porous structure and high pore connectivity. High dye rejection resulted from electrostatic and Donnan repulsions due to surface modification with MPD molecules.

Complexes of Ibuprofen Thiazolidin-4-One Derivatives with β-Cyclodextrin: Characterization and In Vivo Release Profile and Biological Evaluation.

Generally, NSAIDs are weakly soluble in water and contain both hydrophilic and hydrophobic groups. One of the most widely used NSAIDs is ibuprofen, which has a poor solubility and high permeability profile. By creating dynamic, non-covalent, water-soluble inclusion complexes, cyclodextrins (CDs) can increase the dissolution rate of low aqueous solubility drugs, operating as a drug delivery vehicle, additionally contributing significantly to the chemical stability of pharmaceuticals and to reducing drug-related irritability. In order to improve the pharmacological and pharmacokinetics profile of ibuprofen, new thiazolidin-4-one derivatives of ibuprofen (4b, 4g, 4k, 4m) were complexed with β-CD, using co-precipitation and freeze-drying. The new β-CD complexes (β-CD-4b, β-CD-4g, β-CD-4k, β-CD-4m) were characterized using scanning electronic microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction and a phase solubility test. Using the AutoDock-VINA algorithm included in YASARA-structure software, we investigated the binding conformation of ibuprofen derivatives to β-CD and measured the binding energies. We also performed an in vivo biological evaluation of the ibuprofen derivatives and corresponding β-CD complexes, using analgesic/anti-inflammatory assays, as well as a release profile. The results support the theory that β-CD complexes (β-CD-4b, β-CD-4g, β-CD-4k, β-CD-4m) have a similar effect to ibuprofen derivatives (4b, 4g, 4k, 4m). Moreover, the β-CD complexes demonstrated a delayed release profile, which provides valuable insights into the drug-delivery area, focused on ibuprofen derivatives.

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

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

Enabling Stereochemical Communication and Stimuli-Responsive Chiroptical Properties in Biphenyl-Capped Cyclodextrins.

Chiroptical materials are gaining increasing interest due to their innovative character and their applications in optoelectronics and data encryption technologies. Fully harnessing the potential of building blocks from the "chiral pool", such as native cyclodextrins (CDs), as they often lack chromophores suitable for the construction of materials with significant chiroptical properties. Here, we present the synthesis and characterization of a two-level molecular stack consisting of a point-chiral element (CD) and an axially chiral element (biphenyl), capable of effectively translating the overall stereochemical information contained in CDs into stimuli-responsive chiroptical properties. α- and β-permethylated CDs were efficiently capped with two different 2,2'-difunctionalized 1,1'-biphenyl units. In CD derivatives containing the rigid 2,2'-dihydroxy-1,1'-biphenyl cap, two intramolecular hydrogen bonds act synergistically as stereoselective actuators, enabling effective communication between the two levels and the transfer of nonchromophoric stereochemical information from the cyclic-oligosaccharide to the atropoisomeric cap. The chiroptical properties can be finely tuned by external stimuli such as temperature and solvent. The way chirality is transferred from the CD platform to the biphenyl cap was revealed thanks to crystallographic and computational analyses, together with electronic circular dichroism (ECD) studies.

Fast disintegrating dosage forms of mucoadhesive-based nanoparticles for oral insulin delivery: Optimization to in vivo evaluation

The aim of this work was to develop fast disintegrating dosage forms, including fast disintegrating tablets (FDTs) and films (FDFs), for oral insulin delivery incorporating mucoadhesive thiolated chitosan (TCS)-based nanoparticles (NPs). Cyclodextrin (CD)-insulin complexes were formed to prevent insulin from degradation and further optimally prepared NPs in order to improve the mucoadhesive properties. After that, these NPs were incorporated into the dosage forms and then evaluated for their morphology as well as physical and mechanical properties. The disintegration time, insulin content, mucoadhesive properties, insulin release, cytotoxicity, in vivo hypoglycemic effect, and stability of dosage forms were studied. Results showed that the CD-insulin complexes were successfully encapsulated into the mucoadhesive NPs. The 15 %w/w CD-insulin complex-loaded NPs, which were probably dispersed and/or fused into the dosage forms, showed promising characteristics, including rapid disintegration as well as good physical and mechanical properties to withstand erosion during handling and storage. The porous structure of the FDTs promoted liquid flow and induced rapid disintegration. The dosage forms provided buccal mucoadhesion before, during, and/or after the disintegration. The FDFs containing hydroxypropyl β-cyclodextrin (HPβCD)-insulin complex-loaded NPs increased mucoadhesion, increasing insulin release. Furthermore, these dosage forms provided excellent in vivo hypoglycemic response with a prolonged effect in diabetic mice and had no cytotoxicity toward the gingival fibroblast cells. In addition, they were stable at temperatures between 2 and 8 °C for three months. The results indicate that these formulations could be applied as promising dosage forms for use in oral insulin delivery.