Molecular Inclusion Complexes Research Articles

Curcumin- β-Cyclodextrin Molecular Inclusion Complex: A Water- Soluble Complex in Fast-dissolving Tablets for the Treatment of Neurodegenerative Disorders.

Orally disintegrating tablets (ODTs) have become an excellent choice for delivering drugs as their palatability is greatly improved. In this work, β-cyclodextrin has been used to improve the solubility of curcumin by encapsulating it into the hydrophobic cavity for the treatment of neurodegenerative disorders. The current study aimed to present the design, formulation, and optimisation of fastdissolving oral tablets of curcumin- β-cyclodextrin molecular inclusion complex using a 32-factorial design with sodium starch glycolate (SSG) and Neusilin® ULF2 as independent factors. The drug-excipient compatibility was studied by FTIR spectroscopy. The inclusion complex of curcumin-β-cyclodextrin was prepared using solvent casting and confirmed using XRD studies. Powder blends were evaluated for flow properties. Tablets prepared by direct compression were evaluated for post-compression parameters. Further, the effect of formulation variables, such as sodium starch glycolate (X1) and Neusilin® ULF2 (X2), on various responses, including disintegration time and dissolution at 2 hours, was studied using statistical models. Post-compression parameters, i.e., hardness (4.4-5 kg/cm2), thickness (3.82-3.93 mm), weight variation (±7.5%), friability (<1%), wetting time (51-85 seconds) and drug content (96.28- 99.32%) were all found to be within the permissible limits and the disintegration time of tablets with super-disintegrants ranged between 45-58 seconds. The in-vitro dissolution profile of tablets showed that higher SSG and Neuslin® ULF2 levels promoted drug release. For statistical analysis, the 2FI model was chosen. Optimised variables for formulation have been determined and validated with the experimental findings based on the significant desirability factor. The current study reveals the validated curcumin-β-cyclodextrin inclusion Complex fast-dissolving tablets with SSG and Neusilin® ULF2 to be an ideal choice for effectively treating neurodegenerative disorders.

Cascade Bioreactors Based on Host–Guest Molecular Inclusion Complexes for Triple‐Negative Breast Cancer Therapy via Inducing Ferroptosis

AbstractTriple‐negative breast cancer (TNBC) poses significant challenges in tumor treatment. Ferroptosis, as a novel cell death mechanism, holds promise as a potential therapeutic strategy for TNBC. In this study, cascade bioreactors based on host–guest molecular inclusion complexes (PCFP@PL/p53) are constructed for TNBC therapy via inducing ferroptosis. The bioreactors are composed of hydrophobic hemirotaxane (mPEG‐β‐CD/α‐CD) and hydrophilic multi‐branched polyethyleneimine‐ferrocene (PEI‐Fc). They are linked by the reactive oxygen species (ROS)‐responsive molecular switch β‐CD@Fc, which can be activated by high levels of ROS. This activation leads to the rapid disassembly of PCFP@PL/p53 and the subsequent release of the loaded piperlongumine (PL) and p53 plasmids. In addition to acting as a “switch,” Fc can react with hydrogen peroxide (H2O2) in a Fenton reaction to produce hydroxyl radicals. PL decreases intracellular reduced glutathione and induces H2O2 accumulation, which corporates with Fc to launch ferroptosis and activated p53. The activated p53 disrupts the SLC7A11‐GSH‐GPX4 pathway, further increasing the intracellular ROS levels, resulting in a cascade amplification of ROS that ultimately induces massive ferroptosis. Meanwhile, the PCFP@PL/p53‐induced ferroptosis also activates the immune system in vivo, restricting the growth and metastasis of TNBC, thus providing a novel approach for TNBC therapy based on ferroptosis.

A comprehensive study on flavor/cyclodextrin inclusion complexes

Flavors, being highly volatile compounds used in various circumstance, often require encapsulation to facilitate their handling and processing. Among different encapsulation strategies, molecular inclusion complexation with cyclodextrins through host-guest interactions is one of the most commonly employed approach. This study focuses on the fabrication of different kinds of flavor/cyclodextrin inclusion complexes and the identification of inclusion regularities, as well as the prediction of encapsulation results based on the chemical structures and oil-water partition coefficients of flavors. Meanwhile, the property characterizations of representative inclusion complexes confirm improvements in sustained release ability and flavors stability. These inclusion complexes have potential applications in the fields of food and tobacco processing. Furthermore, we successfully prepare the inclusion products with stable loading capacities and yields in a 100 L reactor, suggesting the significant potential for industrial-scaled production using the preparation method for flavor/cyclodextrin inclusion complexes outlined in this study.

Nanofibers of Glycyrrhizin/Hydroxypropyl-β-Cyclodextrin Inclusion Complex: Enhanced Solubility Profile and Anti-inflammatory Effect of Glycyrrhizin.

Despite having a wide range of therapeutic advantages, glycyrrhizin (GL) has few commercial applications due to its poor aqueous solubility. In this study, we combined the benefits of hydroxypropyl β-cyclodextrin (HP-βCD) supramolecular inclusion complexes and electrospun nanofibers to improve the solubility and therapeutic potential of GL. A molecular inclusion complex containing GL and HP-βCD was prepared by lyophilization at a 1:2 molar ratio. GL and hydroxypropyl β-cyclodextrin inclusion complexes were also incorporated into hyaluronic acid (HA) nanofibers. Prepared NF was analyzed for physical, chemical, thermal, and pharmaceutical properties. Additionally, a rat model of carrageenan-induced hind paw edema and macrophage cell lines was used to evaluate the anti-inflammatory activity of GL-HP-βCD NF. The DSC and XRD analyses clearly showed the amorphous state of GL in nanofibers. In comparison to pure GL, GL-HP-βCD NF displayed improved release (46.6 ± 2.16% in 5min) and dissolution profiles (water dissolvability ≤ 6s). Phase solubility results showed a four-fold increase in GL solubility in GL-HP-βCD NF. In vitro experiments on cell lines showed that inflammatory markers like IL-1β, TNF-α, and IL-6 were significantly lower in GL-HP-βCD NF compared to pure GL (p < 0.01 and p < 0.05). According to in vivo results, the prepared nanofiber exhibits a better anti-inflammatory effect than pure GL (63.4% inhibition vs 53.7% inhibition). The findings presented here suggested that GL-HP-βCD NF could serve as a useful strategy for improving the therapeutic effects of GL.

Inclusion Complexes of β-Cyclodextrin with Salvia officinalis Bioactive Compounds and Their Antibacterial Activities

In the present study, the formation of molecular inclusion complexes of Salvia officinalis (sage) bioactive compounds with β-cyclodextrin (β-CD) was evaluated. Sage essential oil (SEO)/β-CD inclusion complexes (ICs) were prepared by co-precipitation at iso-molecular concentrations, and Fourier transform infrared spectroscopy (FT-IR) was applied for the confirmation of the ICs’ formation. Quantification of the SEO in the inclusion complexes was performed spectrophotometrically at 273 nm using an SEO standard curve. The SEO and its inclusion complexes were evaluated for their antimicrobial activity against Escherichia coli, Staphylococcus aureus and Listeria monocytogenes. The results showed that β-CD effectively formed inclusion complexes with SEO in satisfactory yields. The antimicrobial activity of the SEO in prepared complexes with β-CD was exhibited against L. monocytogenes and S. aureus and was proportional to their concentrations but was less pronounced.

Targeted intracellular delivery of antitubercular bioactive(s) to Mtb infected macrophages via transferrin functionalized nanoliposomes

The packaging of antimicrobials/chemotherapeutics into nanoliposomes can enhance their activity while minimizing toxicity. However, their use is still limited owing to inefficient/inadequate loading strategies. Several bioactive(s) which are non ionizable, and poorly aqueous soluble cannot be easily encapsulated into aqueous core of liposomes by using conventional means. Such bioactive(s) however could be encapsulated in the liposomes by forming their water soluble molecular inclusion complex with cyclodextrins. In this study, we developed Rifampicin (RIF) − 2-hydroxylpropyl-β-cyclodextrin (HP-β-CD) molecular inclusion complex. The HP-β-CD-RIF complex interaction was assessed by using computational analysis (molecular modeling). The HP-β-CD-RIF complex and Isoniazid were co-loaded in the small unilamellar vesicles (SUVs). Further, the developed system was functionalized with transferrin, a targeting moiety. Transferrin functionalized SUVs (Tf-SUVs) could preferentially deliver their payload intracellularly in the endosomal compartment of macrophages. In in vitro study on infected Raw 264.7 macrophage cells revealed that the encapsulated bioactive(s) could eradicate the pathogen more efficiently than free bioactive(s). In vivo studies further revealed that the Tf-SUVs could accumulate and maintain intracellular bioactive(s) concentrations in macrophages. The study suggests Tf-SUVs as a promising module for targeted delivery of a drug combination with improved/optimal therapeutic index and effective clinical outcomes.

Estimation of the Controlled Release of Antioxidants from β-Cyclodextrin/Chamomile (Matricaria chamomilla L.) or Milk Thistle (Silybum marianum L.), Asteraceae, Hydrophilic Extract Complexes through the Fast and Cheap Spectrophotometric Technique.

This is the first study on the modeling of the controlled release of the estimated antioxidants (flavonoids or flavonolignans) from β-cyclodextrin (β-CD)/hydrophilic vegetable extract complexes and the modeling of transdermal pharmaceutical formulations based on these complexes using an overall estimation by the spectrophotometric method. The Korsmeyer-Peppas model was chosen for evaluating the release mechanisms. β-CD/chamomile (Matricaria chamomilla L., Asteraceae) ethanolic extract and β-CD/milk thistle (Silybum marianum L., Asteraceae) ethanolic extract complexes were obtained by the co-crystallization method with good recovering yields of 55-76%, slightly lower than for β-CD/silibinin or silymarin complexes (~87%). According to differential scanning calorimetry (DSC) and Karl Fischer water titration (KFT), the thermal stability of complexes is similar to β-CD hydrate while the hydration water content is lower, revealing the formation of molecular inclusion complexes. In the Korsmeyer-Peppas model, β-CD/M. chamomilla flower extract complexes reveal Case II transport mechanisms, while the corresponding complexes with leaf extracts indicate non-Fickian diffusion for the controlled release of antioxidants in ethanol 60 and 96%. The same non-Fickian diffusion was revealed by β-CD/S. marianum extract and β-CD/silibinin complexes. On the contrary, almost all model transdermal pharmaceutical formulations based on β-CD/M. chamomilla extract complexes and all those based on β-CD/S. marianum extract complexes revealed non-Fickian diffusion for the antioxidant release. These results indicate that H-bonding is mainly involved in the diffusion of antioxidants into a β-CD based matrix, while the controlled release of antioxidants in model formulations is mainly due to hydrophobic interactions. Results obtained in this study can be further used for studying the particular antioxidants (namely rutin or silibinin, quantified, for example, by liquid chromatographic techniques) for their transdermal transport and biological effects in innovatively designed pharmaceutical formulations that can be obtained using "green" methods and materials.

Competitive formation of molecular inclusion complexes of chlordecone and β-hexachlorocyclohexane with natural cyclodextrins: DFT and molecular dynamics study.

Chlordecone (CLD) and β-hexachlorocyclohexane (β-HCH) are chlorinated pesticides that coexist as persistent organic pollutants in the groundwater of several countries in the Caribbean, being an environmental issue. This work evaluates theoretically the competitive formation of host-guest complexes pesticides@cyclodextrines (CDs) as an alternative for water purification and selective separation of pesticides. Quantum mechanical calculations based on density functional theory (DFT) and classical molecular dynamics (MD) simulations were used to achieve information on geometries, energies, structure, and dynamics of guest-host complexes in the gas phase, implicit solvent medium, and in aqueous solutions. DFT studies showed that interactions of both pesticides with CDs are mediated by steric factors and guided by maximization of the hydrophobic interactions either with the other pesticide or with the CD cavity's inner atoms. MD results corroborate the formation of stable complexes of both pesticides with the studied CDs. α-CD exhibited a preference for the smaller β-HCH molecule over the CLD that could not perturb the formed complex. The simulation of competitive formation with γ-CD illustrated that this molecule could accommodate both pesticides inside its cavity. These results suggest that CDs with smaller cavity sizes such as α-CD could be used for selective separation of β-HCH from CLD in water bodies, while γ-CD could be used for methods that aim to remove both pesticides at the same time.

Fabrication and Characterization of β-Cyclodextrin/Mosla Chinensis Essential Oil Inclusion Complexes: Experimental Design and Molecular Modeling.

Essential oils (EOs) are primarily isolated from medicinal plants and possess various biological properties. However, their low water solubility and volatility substantially limit their application potential. Therefore, the aim of the current study was to improve the solubility and stability of the Mosla Chinensis (M. Chinensis) EO by forming an inclusion complex (IC) with β-cyclodextrin (β-CD). Furthermore, the IC formation process was investigated using experimental techniques and molecular modeling. The major components of M. Chinensis 'Jiangxiangru' EOs were carvacrol, thymol, o-cymene, and terpinene, and its IC with β-CD were prepared using the ultrasonication method. Multivariable optimization was studied using a Plackett-Burman design (step 1, identifying key parameters) followed by a central composite design for optimization of the parameters (step 2, optimizing the key parameters). SEM, FT-IR, TGA, and dissolution experiments were performed to analyze the physicochemical properties of the ICs. In addition, the interaction between EO and β-CD was further investigated using phase solubility, molecular docking, and molecular simulation studies. The results showed that the optimal encapsulation efficiency and loading capacity of EO in the ICs were 86.17% and 8.92%, respectively. Results of physicochemical properties were different after being encapsulated, indicating that the ICs had been successfully fabricated. Additionally, molecular docking and dynamics simulation showed that β-CD could encapsulate the EO component (carvacrol) via noncovalent interactions. In conclusion, a comprehensive methodology was developed for determining key parameters under multivariate conditions by utilizing two-step optimization experiments to obtain ICs of EO with β-CD. Furthermore, molecular modeling was used to study the mechanisms involved in molecular inclusion complexation.

Piroxicam: 2‐hydroxypropyl‐β‐cyclodextrin complex as corrosion inhibitor for the aluminum anode in extremely alkaline‐based primary batteries

AbstractThe corrosion inhibitive capabilities of an aluminum anode in 6 M KOH solution at 50°C with single piroxicam: 2‐hydroxypropyl‐β‐cyclodextrin molecular inclusion complex (PIR: HP‐β‐CD) and mixed PIR: HP‐β‐CD + Na2SnO3 additives are investigated using hydrogen gas collection, weight loss measurement, electrochemical tests, infrared spectra, and scanning electron microscopy (FESEM). The results indicate that the corrosion inhibition efficiency of PIR: HP‐β‐CD additive is increased to 10 ppm concentration (33%). The PIR: HP‐β‐CD adsorbs on the aluminum surface and impedes the accessibility of water to the surface. On the other hand, using only 0.002 M Na2SnO3 reduced aluminum's anodic dissolution and did not provide sufficient efficiency in inhibiting hydrogen evolution. However, adding 10 PIR: HP‐β‐CD to KOH solution containing 0.002 M Na2SnO3 has created a synergistic effect in corrosion inhibition. The highest electrochemical activity, the lowest hydrogen evolution rate (4.48 ml cm−2 s−1), the highest inhibition efficiency (81.14%), and the highest capacity are attained in the 6 M KOH solution with the mixed additives. Indeed, the 10 ppm PIR: HP‐β‐CD + 0.002 M Na2SnO3 additives could be recommended as an excellent corrosion inhibitor in extremely alkaline electrolytes for the aluminum anode at high current densities.

Encapsulation of volatile oils with antimicrobial activity in chitosan-βCD molecular inclusion complexes by spray drying

Binary and ternary molecular inclusion complexes (MICs) of beta-cyclodextrin (βCD - binary), and chitosan-βCD (ternary) loaded with Lippia sidoides (LS) and Syzygium aromaticum (SA) volatile oils (VOs—pure and in 1:1 mixtures) were engineered by a modified slurry method followed by spray drying. Eugenol and Thymol, the major constituents of SA and LS VOs, were successfully retained in MICs, showing good values of the encapsulation efficiency (EE), molar ratio (MR), and VOs load (DL). EEs were higher for the pure VOs (68.7 ± 1.6 to 86.1 ± 4.0% w/w) compared to their mixtures (37.8 ± 1.4 to 65.9 ± 2.4% w/w). The chitosan addition increased the Thymol’s EE, while for Eugenol, an opposite effect was exhibited. The MICs formed showed slight changes in the volatiles' composition, evidencing a selective encapsulation of the VOs constituents. The effects of processing conditions on moisture content, water activity, and particle size were negligible. The reported results suggest the feasibility of the complexation protocols proposed to manufacture novel binary and ternary complexes of βCD and chitosan.

Recent advances of octenyl succinic anhydride modified polysaccharides as wall materials for nano‐encapsulation of hydrophobic bioactive compounds

Polysaccharides can be esterified with octenyl succinic anhydride (OSA) to form derivatives with amphiphilic properties. The general preparation methods of OSA-polysaccharides are described, especially the aqueous method. The new hydrophobic groups introduced result in OSA-polysaccharides showing higher interfacial properties, better emulsifying stability, higher viscosity, and lower digestibility. There have been advances in the development of OSA-polysaccharides-based nano-encapsulation systems for hydrophobic bioactive compounds in recent years. Nano-encapsulation systems are formed through nanoemulsions, nanocapsules, nanoparticles, micelles, vesicles, molecular inclusion complexes, and so on. This review aims to describe the preparation methods, the structure characterizations, and the physicochemical properties of OSA-polysaccharides as encapsulating agents. In addition, the focus is on the different nano-encapsulation systems based on OSA-polysaccharides as wall materials. Future perspectives will concern OSA-polysaccharides-based nano-encapsulation systems with optimized functional properties for providing higher bioavailability and targeted delivery of various hydrophobic bioactive compounds. © 2022 Society of Chemical Industry.

Genotoxicity and mutagenicity evaluation of isoquercitrin-γ-cyclodextrin molecular inclusion complex using Ames test and a combined micronucleus and comet assay in rats.

Flavonoids such as quercetin and its glucosides, especially isoquercitrin are well known as anti-inflammatory, anti-allergic, and anti-carcinogenic, etc. The safety of isoquercitrin formulations needs to be established prior to their use in functional food applications. The mutagenicity and genotoxicity of the IQC-γCD inclusion complex were assessed with three standard assays of the bacterial reverse mutation assay (Ames test) and using a combined in-vivo micronucleus and comet assay under the Organisation for Economic Co-operation and Development (OECD) guidelines. In combined rat bone marrow micronucleus and rat liver comet assay performed in male Sprague Dawley (SD) rats, the various doses of IQC-γCD inclusion complex (max. 2000 mg/kg bw) and positive controls ethyl methanesulfonate (EMS) and mitomycin C (MMC), respectively, and negative control (vehicle) were administrated. The results of the Salmonella typhimurium mutagenicity assay (strains TA100, TA1535, WP2uvrA, TA98, and TA1537) after exposure to the IQC-γCD inclusion complex with the absence and presence of the metabolic activation system (S9 fraction from rat liver) revealed a weakly positive response but with no biologically relevant mutagenicity at the conditions examined according to recommended regulatory guidelines. The combined micronucleus and comet assay results reveal that the IQC-γCD inclusion complex did not induce in-vivo genotoxic potential or indication of any oxidative DNA damage in rat liver tissues. Altogether, considering the results of the study, it is unlikely that the consumption of IQC-γCD inclusion complex as food or supplement would present any concern for humans regarding the mutagenicity and genotoxicity.

Bioavailability of dietary isoquercitrin-γ-cyclodextrin molecular inclusion complex in Sprague–Dawley rats and healthy humans

• Proprietary IQC-γCD inclusion complex has enhanced bioavailability due to improved solubility. • The bioavailability of IQC-γCD was 3.8-fold higher than that of quercetin in SD rats. • The bioavailability of IQC-γCD was 10.5-fold higher than that of quercetin in healthy humans. • The bioavailability of IQC-γCD was nearly 4-times higher than that of other reported isoquercitrin formulations in humans. • IQC-γCD inclusion complex mainly absorbed as primary metabolites (about 90%) of quercetin in humans. Isoquercitrin has been drawing increasing commercial concern since it has better bioavailability than quercetin and displays a wide range of in-vivo and in-vitro pharmacological effects. The main objective of the present study was to evaluate the pharmacokinetics of the IQC-γCD inclusion complex in Sprague-Dawley (SD) rats and in a controlled non-randomized, double-blind, and crossover study among the healthy volunteers. For instance, in SD rats administrated with IQC-γCD formulation by oral gavage feeding (0.05 mM/Kg body weight) showed significantly higher bioavailability (P < 0.001) of the quercetin and its metabolites compared to quercetin (control) intake. Whereas, in healthy humans (n = 8) an acute administration of IQC-γCD molecular inclusion complex (0.47 mM; the doses corresponds to 2.34 mg quercetin equivalence/Kg body weight) significantly enhanced the plasma conjugated quercetin and its metabolites concentration (P < 0.0001), and exhibited a greater pharmacokinetic profile compared to quercetin embedded in dextrin (control) supplementation. The results indicate an improved bioavailability of quercetin and its metabolites of IQC-γCD inclusion complex compared to respective controls in both animals and humans, wherein intestinal epithelial enzyme lactase-phlorizin hydrolase preferably hydrolyze the isoquercitrin of IQC-γCD inclusion complex to conjugated quercetin and its glucuronides and/or sulfates metabolites. The results also support the useful future applications of IQC-γCD inclusion complex in food additives, health supplements, and functional beverages for health benefits.

Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes.

There is growing evidence that repurposed drugs demonstrate excellent efficacy against many cancers, while facilitating accelerated drug development process. In this study, bedaquiline (BDQ), an FDA approved anti-mycobacterial agent, was repurposed and an inhalable cyclodextrin complex formulation was developed to explore its anti-cancer activity in non-small cell lung cancer (NSCLC). A sulfobutyl ether derivative of β-cyclodextrin (SBE-β-CD) was selected based on phase solubility studies and molecular modeling to prepare an inclusion complex of BDQ and cyclodextrin. Aqueous solubility of BDQ was increased by 2.8 × 103-fold after complexation with SBE-β-CD, as compared to its intrinsic solubility. Solid-state characterization studies confirmed the successful incorporation of BDQ in the SBE-β-CD cavity. In vitro lung deposition study results demonstrated excellent inhalable properties (mass median aerodynamic diameter: 2.9 ± 0.6 µm (<5 µm) and fine particle fraction: 83.3 ± 3.8%) of BDQ-CD complex. Accelerated stability studies showed BDQ-CD complex to be stable up to 3 weeks. From cytotoxicity studies, a slight enhancement in the anti-cancer efficacy was observed with BDQ-cyclodextrin complex, compared to BDQ alone in H1299 cell line. The IC50 values for BDQ and BDQ-CD complex were found to be ~40 µM in case of H1299 cell line at 72 h, whereas BDQ/BDQ-CD were not found to be cytotoxic up to concentrations of 50 µM in A549 cell line. Taken together, BDQ-CD complex offers a promising inhalation strategy with efficient lung deposition and cytotoxicity for NSCLC treatment.

Enantioseparation on a new synthetic β-cyclodextrin chemically bonded chiral stationary phase and molecular docking study.

A novel β-cyclodextrin derivative chemically bonded chiral stationary phase (EDACD) was synthesized by the reaction of mono-6-ethylenediamine-β-cyclodextrin with the active alkyl isocyanate, anchoring to silica gel. After the successful analysis and characterization using scanning electron microscopy, Fourier transform infrared spectra, solid-state nuclear magnetic resonance spectra, elemental analysis, and thermogravimetric analysis techniques, the enantioselective performance of the as-prepared EDACD column was evaluated by non-steroidal antiinflammatory drugs and flavonoids under the reversed-phase HPLC condition. The factors that affected enantioseparation including mobile phase compositions and buffers were investigated in more detail. As a result, EDACD showed a satisfactory enantioselectivity for the tested drugs. With the mobile phase of acetonitrile and 20-mM ammonium formate adjusted to pH4.0 using formic acid (85:15, v/v) at the flow rate of 0.6mLmin-1, the enantiomers of ibuprofen, carprofen, naproxen, indoprofen, ketoprofen, eriocitrin, naringin, and narirutin were separated with the best resolutions of 1.53, 1.64, 3.72, 2.40, 0.50, 0.61, 0.58, and 0.52. To adjust the proportion of acetonitrile to 80% (by volume), the enantiomers of pranoprofen and flurbiprofen were completely resolved with the best resolutions of 1.60 and 1.59. Additionally, by the study of the molecular docking, hydrogen bonding and inclusion complexation were believed to play an important role in chiral recognition. As a new material, EDACD will have a wider application in the analysis of chiral compounds.

13-Weeks subchronic toxicity of isoquercitrin-γ-cyclodextrin (IQC-γCD) molecular inclusion complex in Sprague-Dawley rats

Flavonoids such as quercetin and its glycoside Isoquercitrin and are abundantly present in the diet and have various pharmacological effects. However, limited data about its potential toxicity is available. In this study, we aim to evaluate the subchronic toxicity of the isoquercitrin-γ-cyclodextrin (IQC-γCD) molecular inclusion complex (SunActive® QCD/EN) in Sprague-Dawley (SD) rats. The IQC-γCD was administrated orally to 40 male and 40 female SD rats at dietary doses up to 5.0 % for 13 consecutive weeks. During the experiment periods, the general clinical signs, mortality, hematological, urinalysis values, biochemical, and histopathological parameters were examined. All animals survived until the scheduled necropsy, and no statistically significant or clinical sign of toxicologically relevant differences including pathology parameters, and histopathological endpoints were observed in any of the IQC-γCD treatment groups, compared with the control group. However, certain observations were noted in the male rats treated with the highest concentration (5.0 %), but these were not seen in female rats. A slight inhibition of weight gain was observed, probably linked to a fall in red blood cells, and hematocrit index in female rats. Statistically significant changes were noted in some clinical measures, such as plasma bilirubin level, alkaline phosphatase total bile acid without evidence of systemic clinical toxicity. The results support no observed adverse effect level (NOAEL) of IQC-γCD of 5.0 % in the diet for males (3338.55 mg/kg/day), and 3.0 % in the diet for females (2177.33 mg/kg/day) SD rats. Therefore, in this 13 weeks repeated-dose SD rat study there were no treatment-related adverse clinical or pathological findings for IQC-γCD of 5.0 % in the diet for males, and 3.0 % in the diet for females SD rats. The results of the present study support the safe use of IQC-γCD as a functional food, food additive, and natural ingredient.

Preparation and characterization of native starch-ibuprofen molecular inclusion complexes

Starch is a biodegradable and biocompatible polymer recognized as a versatile starting material for developing innovative drug delivery systems. In this way, the present research work investigates the ability of bamboo and corn starches to carrier ibuprofen via the formation of molecular inclusion complexes by the Acidification of an Alkaline Solution and the Heating-Sealing methods. The water ratio and the reaction time used in each procedure influence the yield and efficiency of complexation; thus, the yield varies between 16.3% and 89.6% for the bamboo starch and between 30.3% and 74.5% for the corn starch. The complexing efficiencies reach values up to 10.30% ± 0.02% when bamboo starch was used and up to 22.35% ± 0.04% for corn starch. The thermal characteristics and the pH-dependent drug release pattern exhibited by the obtained complexes keep a closer relationship with their semicrystalline structures. On this basis, starch complexes arise as promising alternatives to deliver active molecules at the intestinal level and offer attractive possibilities for generating added value to native starch sources like bamboo.

Structural elucidation of novel isoquercitrin-γ-cyclodextrin (IQC-γCD) molecular inclusion complexes of potential health benefits

Isoquercitrin has a higher bioavailability than quercetin and has various pharmacological effects. In the present study, we aim to elucidate the structure of the novel isoquercitrin-γ-cyclodextrin (IQC-γCD) inclusion complex derived through controlled enzymatic hydrolysis of rutin into isoquercitrin in-situ included in γ-cyclodextrin. Several vibrational, electronic and analytical spectral measurement techniques (FTIR, 1H-NMR, 13C-NMR, UV-Vis, DSC, PXRD, Raman spectroscopy, and SEM) were employed. The detailed structural comparison of the IQC-γCD inclusion complex with isolated isoquercitrin revealed the shielding of isoquercitrin –OH groups inside the γ-CD cavity, and thus, confirmed the successful formation of the inclusion complex that exhibit distinct spectroscopic features from both guest and host molecules. The phase-solubility studies showed that isoquercitrin formed a 1:1 stoichiometric inclusion complex with γ-CD. The aqueous solubility of isoquercitrin was significantly enhanced by complexation with γ-CD complex possibly due to increased isoquercitrin dissolution rate compared to the isolated isoquercitrin. The IQC-γCD inclusion could have enhanced pharmacokinetics that will be useful for future applications in functional foods and health benefits.

Encapsulation of Flavours and Fragrances into Polymeric Capsules and Cyclodextrins Inclusion Complexes: An Update.

Flavours and fragrances are volatile compounds of large interest for different applications. Due to their high tendency of evaporation and, in most cases, poor chemical stability, these compounds need to be encapsulated for handling and industrial processing. Encapsulation, indeed, resulted in being effective at overcoming the main concerns related to volatile compound manipulation, and several industrial products contain flavours and fragrances in an encapsulated form for the final usage of customers. Although several organic or inorganic materials have been investigated for the production of coated micro- or nanosystems intended for the encapsulation of fragrances and flavours, polymeric coating, leading to the formation of micro- or nanocapsules with a core-shell architecture, as well as a molecular inclusion complexation with cyclodextrins, are still the most used. The present review aims to summarise the recent literature about the encapsulation of fragrances and flavours into polymeric micro- or nanocapsules or inclusion complexes with cyclodextrins, with a focus on methods for micro/nanoencapsulation and applications in the different technological fields, including the textile, cosmetic, food and paper industries.