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In this work the aggregation behavior of Rumenic acid (RA) is presented for the first time. The results point to a c.m.c. of 35 μM at pH 8 and 25 °C. This behavior can be modified by introducing CDs into the system to encapsulate the RA. The encapsulation process presented a 1:1 stoichiometry in all the cases studied but the complexation constants were strongly dependent on the type of CDs used, the pH and temperature. Firstly, the effect of the type of CD on the encapsulation process was studied. Among the natural and modified CDs analyzed HPβCD was the best for encapsulating RA. The pKa determined for RA was 4.31. The KF showed different behavior below and above 25 °C due to changes in the stoichiometry. Finally, molecular docking calculations provided further insights into how the different interactions influence the complexation constant.

trans-α-Methylstilbene (tMS), a resveratrol analogue, has recently been studied in a search for new bioactivities. However, such studies do not take into account that the poor solubility of tMS in aqueous solutions could affect its bioactivity. For this reason, we propose, for the first time, using cyclodextrins (CDs) as solubilizers to increase tMS solubility, in aqueous solutions. The HPLC-RP results obtained, point to a 1:1 stoichiometry for all the natural (α-, β- and γ-CD) and modified (HPβCD and MβCD) CDs tested. The KFapp (apparent formation constant) for the tMS–CD complexes was seen to be closely dependent on several factors, including the temperature and type of CD. Indeed, the highest KFapp value was obtained for MβCD, while the KFapp decreased with increasing temperature. In addition, the results showed negative entropy (−8.86 × 10−3 ± 0.40 kJ mol−1 K−1) and enthalpy (−16.70 ± 0.98 kJ mol−1) changes and a negative Gibbs free energy value at 25 °C (−14.00 ± 0.55 kJ mol−1) for the encapsulation process. A computational study carried out using molecular docking calculations showed a high degree of correlation between the computed scores and experimental values. Finally, the complexation of trans-stilbene and pinosylvin with HPβCD was compared with tMS.

Introduction Several authors have reported on the different bioactivities of methyl jasmonate (MeJA) stereoisomers. However, no simple, precise and cheap method for separating and identifying them using reversed-phase high performance liquid chromatography (RP-HPLC) has been developed. Objective (1) To create a simple, precise and cheap method for separating and identifying the four stereoisomers present in commercial racemic mixtures of MeJA and (2) to identify the four stereoisomers using molecular docking techniques and coinjection. Materials and Methods – RP-HPLC using a 250 mm C18 column and different proportions of cyclodextrins (CDs) and organic solvents was applied to a commercial sample of racemic MeJA. Results The results show that the best conditions for separating the MeJA stereoisomers are: 20% methanol in the mobile phase, a temperature of 45 °C and a 16 mM concentration of methyl-β-cyclodextrin (M-β-CD). A simple C18 250 mm column and a flow rate of 1.25 mL/min were used. The reduction in the retention time of MeJA observed when M-β-CD is added to the mobile phases was used to determine the complexation constants of the guest/CD complex and compared with the obtained when other CDs were used. The KF for M-β-CD (117.49 ± 5.9 1/M) was obtained with a 1:1 stoichiometry. The four stereoisomers were identified by molecular docking techniques and coinjection of a commercially available rosemary essential oil. Conclusion The new method identified and classified the four stereoisomers of MeJA in the following ordination: (−)epiMeJA, (−)MeJA; (+)MeJA and (+)epiMeJA. These results could be used to improve the elicitation of cell cultures with only the best isomer. Copyright © 2016 John Wiley & Sons, Ltd.

Roflumilast is an orally available inhibitor of phosphodiesterase (PDE) type 4, which is widely used in chronic obstructive pulmonary diseases. However, it has low solubility and adverse effects include diarrhea and nausea. Since its solubilization may improve treatment and, dismissing any adverse effects, its interaction with cyclodextrins (CDs) was studied. The Higuchi-Connors method was used to determine the complexation constant with different CDs, pH values and temperatures. Molecular docking was used to predict interaction between the complexes. An in vitro digestion experiment was carried out to test roflumilast protection. Finally, the photostability of the complex was evaluated. The complex formed with &beta, CD had the highest K11 value (646 &plusmn, 34 M&minus, 1), although this value decreased with increasing temperature. Similarly, K11 decreased as the pH increased. In vitro digestion showed that CDs protect the drug during digestion and even improve its bioaccessibility. Finally, CDs reduced the drug&rsquo, s extreme photosensitivity, originating a fluorescence signal, which is described for first time. The kinetic parameters of the reaction were obtained. This study not only completes the complexation study of roflumilast-CD, but also points to the need to protect roflumilast from light, suggesting that tablets containing the drug might be reformulated.

In this work we used natural and modified cyclodextrins (β-CD and HP-β-CD) as encapsulating agents to improve citronellal properties. Using fluorimetric techniques, its aggregation behavior was studied for the first time. Its critical micellar concentration was seen to vary with the presence of cyclodextrins, which form 1:1 stoichiometry complexes with citronellal. The encapsulation constants and the scores obtained by Molecular Docking were correlated. Chromatographic (GC–MS) and sensory analysis confirmed that cyclodextrins improve the persistence of the aroma. Finally, the antimicrobial effect of citronellal against Escherichia coli and Bacillus subtilis in the presence and absence of cyclodextrins was studied. A combinatorial effect of citronellal, HP-β-cyclodextrin and Glucobay® as an antimicrobial mixture was observed. The results of this study not only demonstrated the potential of CD mixtures, but also that the growth caused by CD digestion may sometimes be greater that the antimicrobial effect of the agents used in this study.

Resveratrol and oxyresveratrol are natural polyphenolic stilbenes with several important pharmacological activities. However, low solubility and aqueous instability are the major limitations in their drug delivery applications. In the present work, we demonstrated the encapsulation of resveratrol and oxyresveratrol with nanosponge to improve solubility and stability. Several characterization techniques were used to confirm the encapsulation of both drug molecules within the nanosponges. The high encapsulation efficiency of resveratrol (77.73%) and oxyresveratrol (80.33%) was achieved within the nanosponges. Transmission electron microscopy suggested uniform spherical size particles of resveratrol and oxyresveratrol loaded nanosponges. Compared to free drugs, better protection against UV degradation was observed for resveratrol-loaded nanosponge (2-fold) and oxyresveratrol-loaded nanosponge (3-fold). Moreover, a higher solubilization of resveratrol- and oxyresveratrol-loaded nanosponges lead to a better antioxidant activity compared to drug molecules alone. Cytotoxicity studies against DU-145 prostate cancer cell lines further suggested improved activity of both resveratrol and oxyresveratrol-loaded nanosponges without any significant toxicity of blank nanosponges.

The use of betalains as bioactive compounds has been widely investigated. However, their use as a functional food requires a more exhaustive study because of their photosensitivity and poor stability. For this reason, this works studies the stabilization of two highly bioactive betalain derivatives, phenylethylamine-betaxanthin (Ph-Bx) and indoline-betacyanin (In-Bc) by nanoencapsulation in natural a modified cyclodextrins (CDs). Methyl-β-CD (Mβ-CD) showed the best results for Ph-Bx while Hydroxypropyl-β-CD (HPβ-CD) was better in the case of In-Bc. In addition, the effect of pH and temperature on encapsulation was studied finding that the encapsulation constant (KF) value increased as the pH decreased in the case of Ph-Bx but not in the case of In-Bc. The KF decreased as the temperatures increased. The thermodynamic parameters, ΔH°, ΔS° and ΔG°, were also calculated. Molecular docking provided further insight into how the different interactions influenced the encapsulation constant. The results show that the presence of CDs during the biotechnological synthesis of Ph-Bx and In-Bc increased production by 51 and 26%, respectively, and also increased the stability of both derivatives. This study represents a first step towards increasing the production of this type of compound for introduction into functional foods.

Niemann Pick disease Type C (NPC) is a recessive rare disease caused by the mutation on NPC1 and/or NPC2 genes changing the processing of the Low-density proteins (LDL) resulting in an accumulation of lipids in the cells. Until today there is not a cure, the current treatment is based on palliative affairs to reduce the symptoms and prevent its appearance. Among all the treatments proposed the use of cyclodextrins (CDs), nanocarriers which can complex cholesterol, is one of the most useful alternatives. Indeed, for several years 2-hydroxypropyl-β-CD (HPβ-CD) is approved as orphan drug for FDA and EMA to the treatment. However, different CDs based materials are created each year to improve the cholesterol uptake. This review is focused on the novelty of CD based materials for NPC treatment.

The complexation of the bioactive compound oxyresveratrol (OXY) with a polymer called cyclodextrin-based nanosponge (CD-NS) and its application was studied.A new methodology is used to calculate, an apparent inclusion complex constant (KFapp) between a ligand and CD-NSs. Moreover, the KFapp of resveratrol was also evaluated and compared. The complex of OXY with the nanosponge β-CDI 1:4, was studied in vitro using DSC, TGA and FTIR techniques and its drug loading and release behavior were studied. An in vitro digestion showed higher protection of OXY complexed than free OXY. The bioactivity enhancing capacity of OXY was also studied against prostate (PC-3) and colon (HT-29 and HCT-116) cancer cell lines, where it showed stronger cell viability inhibition than the free drug. The findings as a whole represent a new opportunity for studying the complexation of drugs in CD-NSs and the use of oxyresveratrol as an ingredient in nutraceutical products.

Current HPLC methods for analyzing cAMP Phosphodiesterase activity (PDE) use salts, limiting the life of the columns. For this reason, we have developed an improved “ion pairing agent free” method, using a simple 150 mm C18-hydro column at 30 °C and two phases: (a) water with 0.1% acetic acid and (b) 85/15 w/w MeOH/tetrahydrofuran with 0.1% acetic acid. Using this method the peaks for cAMP and AMP were obtained with good resolution (R ≈ 1.35) and sensitivity (5·10−9 mols) in only 15 min. Moreover, the method was applied to the GMP/cGMP pair obtaining the same sensitivity and resolution (R ≈ 1.38). The precision and accuracy were tested and the method was verified with a Type IV Phosphodiesterase reaction, which produced AMP from cAMP. The method is cleaner and less aggressive, and represents an interesting alternative to currently used methods.

The food industry needs cheap, fast and sensitive methods to increase the number of analyses that are routinely carried out; for this reason, new methods are constantly being sought. This paper describes a novel fluorescent nanosensor based on cyclodextrin (CD) to determine ellagic acid (EA). The encapsulation of EA in the presence of borax was studied. Firstly, the complexation of EA–borax was tested. The stoichiometry of the EA–borax complex showed a 1 : 2 complex, with KF1 = 2548 ± 127 M−1 and KF2 = 302 ± 15 M−1. Different CDs were used to obtain a 1 : 1 : 1 CD–EA–borax complex with γ-CD providing the best complexation constant (KF3 = 364 ± 18 M−1). Furthermore, when the accuracy and sensitivity of the nanosensor were tested using a crude blueberry extract, the CD/borax mixture provided an 18 times stronger signal than with the crude extract alone and 7 times stronger than that obtained using borax alone.

Several authors have reported on the different bioactivities of methyl jasmonate (MeJA) stereoisomers. However, no simple, precise and cheap method for separating and identifying them using reversed-phase high performance liquid chromatography (RP-HPLC) has been developed.(1) To create a simple, precise and cheap method for separating and identifying the four stereoisomers present in commercial racemic mixtures of MeJA and (2) to identify the four stereoisomers using molecular docking techniques and coinjection. Materials and Methods - RP-HPLC using a 250 mm C18 column and different proportions of cyclodextrins (CDs) and organic solvents was applied to a commercial sample of racemic MeJA.The results show that the best conditions for separating the MeJA stereoisomers are: 20% methanol in the mobile phase, a temperature of 45 °C and a 16 mM concentration of methyl-β-cyclodextrin (M-β-CD). A simple C18 250 mm column and a flow rate of 1.25 mL/min were used. The reduction in the retention time of MeJA observed when M-β-CD is added to the mobile phases was used to determine the complexation constants of the guest/CD complex and compared with the obtained when other CDs were used. The KThe new method identified and classified the four stereoisomers of MeJA in the following ordination: (-)epiMeJA, (-)MeJA; (+)MeJA and (+)epiMeJA. These results could be used to improve the elicitation of cell cultures with only the best isomer. Copyright © 2016 John WileySons, Ltd.

In this work, an in-depth study of the interaction between piceatannol (a type of stilbene with high biological activity) and different natural and modified cyclodextrins (CDs) is made, using steady state fluorescence. This bioactive molecule forms a 1 : 1 complex with all the natural (α-CD, β-CD and γ-CD) and modified (HP-β-CD, HE-β-CD and M-β-CD) CDs tested. Among natural CDs, the interaction of piceatannol with β-CD was the most efficient. However, the modified CDs showed higher encapsulation constants (KF) than β-CD, except M-β-CD; the highest KF being found for HP-β-CD (14 048 ± 702 M(-1)). The encapsulation of piceatannol in the internal cavity of CDs showed a strong dependence on pH and temperature. The interaction between HP-β-CD and piceatannol was less effective in the pH region where the stilbene begins to suffer the deprotonation of its hydroxyl group. Moreover, the values of KF decreased as the system temperature increased. To obtain information on the mechanism involved in the piceatannol affinity for CD, the thermodynamic parameters of the complexation (ΔH°, ΔS° and ΔG°) were studied, the results showed a negative entropy (-3.7 ± 0.2 J mol(-1) K(-1)), enthalpy (-24.6 ± 1.2 kJ mol(-1)) and Gibbs free energy change at 25 °C (-23.5 ± 1.2 J mol(-1)). Finally, molecular docking calculations provided further insights into how the different interactions influence the complexation constant. A high degree of correlation was observed between the computed scores and experimental values.