Beneficial Effects of Resveratrol and γ-Cyclodextrin on the Hematological and Biochemical Parameters of Healthy Wistar Rats Treated with Cisplatin: A PCA Approach.

It is well known that platinum-based antineoplastic agents, including cisplatin (CP), have side effects that limit their use. Nefrotoxicity, neurotoxicity, and hemolytic anemia are the most common side effects. There are few studies on the reduction in these effects that involves nanoencapsulation; however, almost none involve cyclodextrins (CDs). Changes in the hematological and biochemical parameters of healthy Wistar rats treated with solutions of γ-cyclodextrin/resveratrol/cisplatin (γ-CD/Rv/CP) ternary complexes are investigated for the first time. They are intraperitoneally injected with γ-CD/Rv/CP solutions containing 5 mg CP/kg.b.w. Single shots were administered to six groups of Wistar rats (six individuals for every group) using γ-CD/Rv/CP, γ-CD/CP, γ-CD/Rv complexes, as well as positive- and negative-control groups, respectively. Thirty-two hematological and biochemical parameters were evaluated from blood samples and used as input variables for the principal component analysis (PCA) discrimination of the groups. The best protection was obtained for the γ-CD/Rv/CP ternary complex, which determined closer biochemical values to the control group. These values significantly differ from those of the γ-CD/CP treated group, especially for the IP, UA, and T-Pro kidney-related biochemical parameters. This finding proves the beneficial influence of Rv during CP administration through CD-based carriers.

Estimation of the Controlled Release of Antioxidants from ß-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 ß-cyclodextrin (ß-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. ß-CD/chamomile (Matricaria chamomilla L., Asteraceae) ethanolic extract and ß-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 ß-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 ß-CD hydrate while the hydration water content is lower, revealing the formation of molecular inclusion complexes. In the Korsmeyer-Peppas model, ß-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 ß-CD/S. marianum extract and ß-CD/silibinin complexes. On the contrary, almost all model transdermal pharmaceutical formulations based on ß-CD/M. chamomilla extract complexes and all those based on ß-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 ß-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.

Discrimination of ß-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis.

The goal of the study was the discrimination of ß-cyclodextrin (ß-CD)/hazelnut (Corylus avellana L.) oil/antioxidant ternary complexes through Fourier-transform infrared spectroscopy coupled with principal component analysis (FTIR-PCA). These innovative complexes combine the characteristics of the three components and improve the properties of the resulting material such as the onsite protection against oxidative degradation of hazelnut oil unsaturated fatty acid glycerides. Also, the apparent water solubility and bioaccessibility of the hazelnut oil components and antioxidants can be increased, as well as the controlled release of bioactive compounds (fatty acid glycerides and antioxidant flavonoids, namely hesperidin, naringin, rutin, and silymarin). The appropriate method for obtaining the ternary complexes was kneading the components at various molar ratios (1:1:1 and 3:1:1 for ß-CD hydrate:hazelnut oil (average molar mass of 900 g/mol):flavonoid). The recovering yields of the ternary complexes were in the range of 51.5-85.3% and were generally higher for the 3:1:1 samples. The thermal stability was evaluated by thermogravimetry and differential scanning calorimetry. Discrimination of the ternary complexes was easily performed through the FTIR-PCA coupled method, especially based on the stretching vibrations of CO groups in flavonoids and/or CO/CC groups in the ternary complexes at 1014.6 (± 3.8) and 1023.2 (± 1.1) cm-1 along the second PCA component (PC2), respectively. The wavenumbers were more appropriate for discrimination than the corresponding intensities of the specific FTIR bands. On the other hand, ternary complexes were clearly distinguishable from the starting ß-CD hydrate along the first component (PC1) by all FTIR band intensities and along PC2 by the wavenumber of the asymmetric stretching vibrations of the CH groups at 2922.9 (± 0.4) cm-1 for ternary complexes and 2924.8 (± 1.4) cm-1 for ß-CD hydrate. The first two PCA components explain 70.38% from the variance of the FTIR data (from a total number of 26 variables). Other valuable classifications were obtained for the antioxidant flavonoids, with a high similarity for hesperidin and naringin, according to FTIR-PCA, as well as for ternary complexes depending on molar ratios. The FTIR-PCA coupled technique is a fast, nondestructive and cheap method for the evaluation of quality and similarity/characteristics of these new types of cyclodextrin-based ternary complexes having enhanced properties and stability.

FTIR-PCA Approach on Raw and Thermally Processed Chicken Lipids Stabilized by Nano-Encapsulation in ß-Cyclodextrin.

This study evaluated similarities/dissimilarities of raw and processed chicken breast and thigh lipids that were complexed by ß-cyclodextrin, using a combined FTIR-PCA technique. Lipid fractions were analyzed as non-complexed and ß-cyclodextrin-complexed samples via thermogravimetry, differential scanning calorimetry and ATR-FTIR. The lipid complexation reduced the water content to 7.67-8.33%, in comparison with the ß-cyclodextrin hydrate (~14%). The stabilities of the complexes and ß-cyclodextrin were almost the same. ATR-FTIR analysis revealed the presence of important bands that corresponded to the C=O groups (1743-1744 cm-1) in both the non-complexed and nano-encapsulated lipids. Furthermore, the bands that corresponded to the vibrations of double bonds corresponding to the natural/degraded (cis/trans) fatty acids in lipids appeared at 3008-3011 and 938-946 cm-1, respectively. The main FTIR bands that were involved in the discrimination of raw and processed chicken lipids, and of non-complexed and complexed lipids, were evaluated with PCA. The shifting of specific FTIR band wavenumbers had the highest influence, especially vibrations of the α(1→4) glucosidic bond in ß-cyclodextrin for PC1, and CH2/3 groups from lipids for PC2. This first approach on ß-cyclodextrin nano-encapsulation of chicken lipids revealed the possibility to stabilize poultry fatty components for further applications in various ingredients for the food industry.

Antioxidant Activity and Discrimination of Organic Apples (Malus domestica Borkh.) Cultivated in the Western Region of Romania: A DPPH· Kinetics-PCA Approach.

Apple (Malus domestica Borkh.) is one of the most used fruit for beverages in Romania. The goal of the study was to evaluate the antioxidant activity and discrimination of various parts of organic and non-organic apple varieties cultivated in the western region of Romania using the DPPH kinetics-PCA (principal component analysis) approach. Organic and non-organic apples were subjected to solid-liquid ethanol extraction. Core and shell extracts were mixed with DPPH· and spectrophotometrically monitored at 517 nm. Antioxidant activity and mean DPPH· reaction rate at various time ranges reveal significant differences between organic and non-organic samples, as well as apple parts. Organic core and shell extracts had higher antioxidant activities than the corresponding non-organic samples (74.5-96.9% and 61.9-97.2%, respectively, 23.5-94.3% and 59.5-95.5%). Significant differences were observed for the DPPH· reaction rate for the first ½ min, especially in the presence of organic core extracts (3.7-4.8 µM/s). The organic samples were well discriminated by DPPH· kinetics-PCA, the most important variables being the DPPH· reaction rate for the first time range. This is the first DPPH· kinetics-PCA approach applied for discriminating between organic and non-organic fruits and can be useful for evaluating the quality of such type of fruits.

A DPPH· Kinetic Approach on the Antioxidant Activity of Various Parts and Ripening Levels of Papaya (Carica papaya L.) Ethanolic Extracts.

Papaya fruits (Carica papaya L.) are valuable both as food, including concentrates and mixed beverages and in traditional medicine. The goal of the study was to evaluate the antioxidant activity of various parts of unripe and ripe papaya fruit from the DPPH· kinetics point of view. Peel, pulp, seed, and seed-pulp of unripe and ripe papaya fruits (» and >¾ level of ripening) were extracted with ethanol and monitored at 517 nm in the presence of DPPH·. The radical scavenging capacity (RSC) at various time ranges and DPPH· reaction rates for specific time intervals were determined. The highest RSC values were obtained for papaya pulp extracts, consistently higher for the ripe samples in comparison with the unripe ones (86.4% and 41.3%). The DPPH· rates significantly differ for the unripe and ripe papaya extracts, especially for the first time range. They are more than double for the ripe papaya. These values were 2.70, 4.00, 3.25, 2.75 µM/s for the peel, pulp, seed, seed-pulp extracts from the ripe papaya and only 1.00, 1.65, 1.40, 1.80 µM/s for the unripe samples. DPPH· kinetic approach can be useful for a fast and simple evaluation of the overall antioxidant properties of fruit extracts.