Mechanochemical Approach to Obtaining a Multicomponent Fisetin Delivery System Improving Its Solubility and Biological Activity.

In this study, binary amorphous solid dispersions (ASDs, fisetin-Eudragit®) and ternary amorphous solid inclusions (ASIs, fisetin-Eudragit®-HP-ß-cyclodextrin) of fisetin (FIS) were prepared by the mechanochemical method without solvent. The amorphous nature of FIS in ASDs and ASIs was confirmed using XRPD (X-ray powder diffraction). DSC (Differential scanning calorimetry) confirmed full miscibility of multicomponent delivery systems. FT-IR (Fourier-transform infrared analysis) confirmed interactions that stabilize FIS's amorphous state and identified the functional groups involved. The study culminated in evaluating the impact of amorphization on water solubility and conducting in vitro antioxidant assays: 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)-ABTS, 2,2-diphenyl-1-picrylhydrazyl-DPPH, Cupric Reducing Antioxidant Capacity-CUPRAC, and Ferric Reducing Antioxidant Power-FRAP and in vitro neuroprotective assays: inhibition of acetylcholinesterase-AChE and butyrylcholinesterase-BChE. In addition, molecular docking allowed for the determination of possible bonds and interactions between FIS and the mentioned above enzymes. The best preparation turned out to be ASI_30_EPO (ASD fisetin-Eudragit® containing 30% FIS in combination with HP-ß-cyclodextrin), which showed an improvement in apparent solubility (126.5 ± 0.1 µg∙mL-1) and antioxidant properties (ABTS: IC50 = 10.25 µg∙mL-1, DPPH: IC50 = 27.69 µg∙mL-1, CUPRAC: IC0.5 = 9.52 µg∙mL-1, FRAP: IC0.5 = 8.56 µg∙mL-1) and neuroprotective properties (inhibition AChE: 39.91%, and BChE: 42.62%).

Myricetin Amorphous Solid Dispersions-Antineurodegenerative Potential.

Our research aimed to develop an amorphous solid dispersion (ASD) of myricetin (MYR) with Polyvinylpyrrolidone K30 (PVP30) to enhance its solubility, dissolution rate, antioxidant, and neuroprotective properties. Employing a combination of solvent evaporation and freeze drying, we successfully formed MYR ASDs. XRPD analysis confirmed complete amorphization in 1:8 and 1:9 MYR-PVP weight ratios. DSC thermograms exhibited a single glass transition (Tg), indicating full miscibility. FT-IR results and molecular modeling confirmed hydrogen bonds stabilizing MYR's amorphous state. HPLC analysis indicated the absence of degradation products, ensuring safe MYR delivery systems. Solubility, dissolution rate (pH 1.2 and 6.8), antioxidant (ABTS, DPPH, CUPRAC, and FRAP assays), and in vitro neuroprotective activities (inhibition of cholinesterases: AChE and BChE) were significantly improved compared to the pure compound. Molecular docking studies revealed that MYR had made several hydrogen, hydrophobic, and π-π stacking interactions, which could explain the compound's potency to inhibit AChE and BChE. MYR-PVP 1:9 w/w ASD has the best solubility, antioxidant, and neuroprotective activity. Stability studies confirmed the physical stability of MYR-PVP 1:9 w/w ASD immediately after dissolution and for two months under ambient conditions. Our study showed that the obtained ASDs are promising systems for the delivery of MYR with the potential for use in alleviating the symptoms of neurodegenerative diseases.

How Does Radiation Affect Curcumin Raw Material?

Turmeric, known for its curcuminoid-rich rhizome, particularly curcumin, exhibits notable antioxidant and antiviral properties. The likelihood of microbial contamination necessitates finding reliable techniques for subjecting the sample to radiation from this plant-based raw material. One alternative is to expose curcumin to radiation (e-beam), which was carried out as part of this research. Confirmation of the lack of curcumin decomposition was carried out using HPLC-DAD/MS techniques. Additionally, using the EPR technique, the generated free radicals were defined as radiation effects. Using a number of methods to assess the ability to scavenge free radicals (DPPH, ABTS, CUPRAC, and FRAP), a slight decrease in the activity of curcumin raw material was determined. The analysis of the characteristic bands in the FT-IR spectra allowed us to indicate changes in the phenolic OH groups as an effect of the presence of radicals formed.

Enhanced Antioxidant and Neuroprotective Properties of Pterostilbene (Resveratrol Derivative) in Amorphous Solid Dispersions.

In this study, amorphous solid dispersions (ASDs) of pterostilbene (PTR) with polyvinylpyrrolidone polymers (PVP K30 and VA64) were prepared through milling, affirming the amorphous dispersion of PTR via X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Subsequent analysis of DSC thermograms, augmented using mathematical equations such as the Gordon-Taylor and Couchman-Karasz equations, facilitated the determination of predicted values for glass transition (Tg), PTR's miscibility with PVP, and the strength of PTR's interaction with the polymers. Fourier-transform infrared (FTIR) analysis validated interactions maintaining PTR's amorphous state and identified involved functional groups, namely, the 4'-OH and/or -CH groups of PTR and the C=O group of PVP. The study culminated in evaluating the impact of amorphization on water solubility, the release profile in pH 6.8, and in vitro permeability (PAMPA-GIT and BBB methods). In addition, it was determined how improving water solubility affects the increase in antioxidant (ABTS, DPPH, CUPRAC, and FRAP assays) and neuroprotective (inhibition of cholinesterases: AChE and BChE) properties. The apparent solubility of the pure PTR was ~4.0 µg·mL-1 and showed no activity in the considered assays. For obtained ASDs (PTR-PVP30/PTR-PVPVA64, respectively) improvements in apparent solubility (410.8 and 383.2 µg·mL-1), release profile, permeability, antioxidant properties (ABTS: IC50 = 52.37/52.99 µg·mL-1, DPPH: IC50 = 163.43/173.96 µg·mL-1, CUPRAC: IC0.5 = 122.27/129.59 µg·mL-1, FRAP: IC0.5 = 95.69/98.57 µg·mL-1), and neuroprotective effects (AChE: 39.1%/36.2%, BChE: 76.9%/73.2%) were confirmed.

The Study of Amorphous Kaempferol Dispersions Involving FT-IR Spectroscopy.

Attenuated total reflection-Mid-Fourier transform-infrared (ATR-Mid-FT-IR) spectroscopy combined with principal component analysis (PCA) has been applied for the discrimination of amorphous solid dispersion (ASD) of kaempferol with different types of Eudragit (L100, L100-55, EPO). The ASD samples were prepared by ball milling. Training and test sets for PCA consisted of a pure compound, physical mixture, and incomplete/complete amorphous solid dispersion. The obtained results confirmed that the range 400-1700 cm-1 was the major contributor to the variance described by PC1 and PC2, which are the fingerprint region. The obtained PCA model selected fully amorphous samples as follows: five for KMP-EL100, two for KMP-EL100-55, and six for KMP-EPO (which was confirmed by the XRPD analysis). DSC analysis confirmed full miscibility of all ASDs (one glass transition temperature). FT-IR analysis confirmed the formation of hydrogen bonds between the -OH and/or -CH groups of KMP and the C=O group of Eudragits. Amorphization improved the solubility of kaempferol in pH 6.8, pH 5.5, and HCl 0.1 N.

Genistein Co-Amorphous Systems with Amino Acids: An Investigation into Enhanced Solubility and Biological Activity.

Genistein, an isoflavone known for its antioxidant and antidiabetic effects, suffers from the drawback of low solubility. To overcome this limitation, co-amorphous systems were synthesized by incorporating amino acids that were chosen through computational methods. The confirmation of the amorphous state of lysine and arginine-containing systems was ascertained by X-ray powder diffraction. Subsequently, the characterization of these systems was extended by employing thermo-gravimetry, differential scanning calorimetry, Fourier-transform infrared spectroscopy, and scanning electron microscopy. The investigation also included an assessment of the physical stability of the samples during storage. The apparent solubility of the systems was studied in an aqueous medium. To evaluate the in vitro permeability through the gastrointestinal tract, the parallel artificial membrane permeability assay was employed. The biological properties of the systems were assessed with regard to their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl and cupric ion-reducing antioxidant capacity assays, as well as their ability to inhibit α-glucosidase. The systems' glass transition temperatures were determined, and their homogeneity confirmed via differential scanning calorimetry analysis, while Fourier-transform infrared spectroscopy analysis provided data on molecular interactions. Stability was maintained for the entire 6-month storage duration. The co-amorphous system containing lysine displayed the most pronounced apparent solubility improvement, as well as a significant enhancement in antioxidant activity. Notably, both systems demonstrated superior α-glucosidase inhibition relative to acarbose, a standard drug for managing type 2 diabetes. The results indicate that co-amorphous systems with lysine and arginine have the potential to significantly enhance the solubility and biological activity of genistein.

Screening of the Anti-Neurodegenerative Activity of Caffeic Acid after Introduction into Inorganic Metal Delivery Systems to Increase Its Solubility as the Result of a Mechanosynthetic Approach.

The proven anti-neurodegenerative properties of caffeic acid in vivo are limited due to its poor solubility, which limits bioavailability. Therefore, caffeic acid delivery systems have been developed to improve caffeic acid solubility. Solid dispersions of caffeic acid and magnesium aluminometasilicate (Neusilin US2-Neu) were prepared using the ball milling and freeze-drying techniques. The solid dispersions of caffeic acid:Neu obtained by ball milling in a 1:1 mass ratio turned out to be the most effective. The identity of the studied system in comparison to the physical mixture was confirmed using the X-Ray Powder Diffractionand Fourier-transform infrared spectroscopy techniques. For caffeic acid with improved solubility, screening tests were carried out to assess its anti-neurodegenerative effect. The obtained results on the inhibition of acetylcholinesterase, butyrylcholinesterase, tyrosinase, and antioxidant potential provide evidence for improvement of caffeic acid's anti-neurodegenerative activity. As a result of in silico studies, we estimated which caffeic acid domains were involved in interactions with enzymes showing expression relevant to the neuroprotective activity. Importantly, the confirmed improvement in permeability of the soluble version of caffeic acid through membranes simulating the walls of the gastrointestinal tract and blood-brain barrier further strengthen the credibility of the results of in vivo anti-neurodegenerative screening tests.

Amorphous Pterostilbene Delivery Systems Preparation-Innovative Approach to Preparation Optimization.

The aim of our research was to improve the solubility and antioxidant activity of pterostilbene (PTR) by developing a novel amorphous solid dispersion (ASD) with Soluplus® (SOL). DSC analysis and mathematical models were used to select the three appropriate PTR and SOL weight ratios. The amorphization process was carried out by a low-cost and green approach involving dry milling. An XRPD analysis confirmed the full amorphization of systems in 1:2 and 1:5 weight ratios. One glass transition (Tg) observed in DSC thermograms confirmed the complete miscibility of the systems. The mathematical models indicated strong heteronuclear interactions. SEM micrographs suggest dispersed PTR within the SOL matrix and a lack of PTR crystallinity, and showed that after the amorphization process, PTR-SOL systems had a smaller particle size and larger surface area compared with PTR and SOL. An FT-IR analysis confirmed that hydrogen bonds were responsible for stabilizing the amorphous dispersion. HPLC studies showed no decomposition of PTR after the milling process. PTR's apparent solubility and antioxidant activity after introduction into ASD increased compared to the pure compound. The amorphization process improved the apparent solubility by ~37-fold and ~28-fold for PTR-SOL, 1:2 and 1:5 w/w, respectively. The PTR-SOL 1:2 w/w system was preferred due to it having the best solubility and antioxidant activity (ABTS: IC50 of 56.389 ± 0.151 µg·mL-1 and CUPRAC: IC0.5 of 82.52 ± 0.88 µg·mL-1).

Sinapic Acid Co-Amorphous Systems with Amino Acids for Improved Solubility and Antioxidant Activity.

The objective of this study was to obtain co-amorphous systems of poorly soluble sinapic acid using amino acids as co-formers. In order to assess the probability of the interaction of amino acids, namely, arginine, histidine, lysine, tryptophan, and proline, selected as co-formers in the amorphization of sinapic acid, in silico studies were carried out. Sinapic acid systems with amino acids in a molar ratio of 1:1 and 1:2 were obtained using ball milling, solvent evaporation, and freeze drying techniques. X-ray powder diffraction results confirmed the loss of crystallinity of sinapic acid and lysine, regardless of the amorphization technique used, while remaining co-formers produced mixed results. Fourier-transform infrared spectroscopy analyses revealed that the co-amorphous sinapic acid systems were stabilized through the creation of intermolecular interactions, particularly hydrogen bonds, and the potential formation of salt. Lysine was selected as the most appropriate co-former to obtain co-amorphous systems of sinapic acid, which inhibited the recrystallization of sinapic acid for a period of six weeks in 30 °C and 50 °C. Obtained co-amorphous systems demonstrated an enhancement in dissolution rate over pure sinapic acid. A solubility study revealed a 12.9-fold improvement in sinapic acid solubility after introducing it into the co-amorphous systems. Moreover, a 2.2-fold and 1.3-fold improvement in antioxidant activity of sinapic acid was observed with respect to the ability to neutralize the 2,2-diphenyl-1-picrylhydrazyl radical and to reduce copper ions, respectively.

Do Rutin and Quercetin Retain Their Structure and Radical Scavenging Activity after Exposure to Radiation?

The influence of ionizing radiation on the physicochemical properties of quercetin and rutin in the solid state was studied. Quercetin and rutin were irradiated with the standard recommended radiation dose (25 kGy) according to EN 522 standard. The samples were irradiated by electron beam radiation. EPR studies indicate the formation of a small number of free radicals due to irradiation. Moreover, some radicals recombined with the mean lifetime of 1200 and 93 h, and a stable radical concentration reached only 0.29 and 0.90 ppm for quercetin and rutin, respectively. The performed spectroscopic study (FT-IR) confirmed the radiostability of the flavonoids tested. Chromatographic tests (HPLC, HPLC-MS) showed that irradiation of quercetin and rutin with a 25 kGy dose did not change the physicochemical properties of the tested compounds. Degradation products were not observed. The antioxidant activities were determined by the 2,2-diphenyl-1-pycrylhydrazyl (DPPH) free radical scavenging activity assay, ABTS Radical Scavenging Assay (ABTS), Ferric Reducing Antioxidant Power Assay (FRAP), Cupric Ion Reducing Antioxidant Capacity Assay (CUPRAC). The conducted research confirmed that exposure to ionizing radiation does not change the chemical structure of tested flavonoids and their antioxidant properties.

Pleiotropic Potential of Evernia prunastri Extracts and Their Main Compounds Evernic Acid and Atranorin: In Vitro and In Silico Studies.

Evernia prunastri is a lichen widely distributed in the Northern Hemisphere. Its biological properties still need to be discovered. Therefore, our paper focuses on studies of E. prunastri extracts, including its main metabolites evernic acid (EA) or atranorin (ATR). Phytochemical profiles using chromatographic analysis were confirmed. The antioxidant activity was evaluated using in vitro chemical tests and in vitro enzymatic cells-free tests, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and catalase (CAT). The anti-inflammatory potential using cyclooxygenase-2 (COX-2) and hyaluronidase were determined. The neuroprotective potential using acetylcholinesterase, (AChE), butyrylcholinesterase (BChE), and tyrosinase (Tyr) was estimated. The hypoglycemic activity was also confirmed (α-glucosidase). Principal component analysis was performed to determine the relationship between the biological activity of extracts. The inhibitory effect of EA and ATR on COX-2 AChE, BChE, Tyr, and α-glucosidase was evaluated using molecular docking techniques and confirmed for EA and ATR (besides α-glucosidase). The penetration of EA and ATR from extracts through the blood-brain barrier was confirmed using the parallel artificial membrane permeability assay blood-brain barrier test. In conclusion, depending on chemical surroundings and the concentration, the E. prunastri extracts, EA or ATR, showed attractive pleiotropic properties, which should be further investigated.

A Fisetin Delivery System for Neuroprotection: A Co-Amorphous Dispersion Prepared in Supercritical Carbon Dioxide.

Fisetin (FIS), a senolytic flavonoid, mitigates age-related neuroprotective changes. An amorphous FIS dispersion with a co-carrier was prepared using supercritical fluid extraction with carbon dioxide (scCO2). Characterisation, including powder X-ray diffraction and Fourier-transform infrared spectroscopy, confirmed amorphization and assessed intermolecular interactions. The amorphous FIS dispersion exhibited enhanced solubility, dissolution profiles, and bioavailability compared to the crystalline form. In vitro, the amorphous FIS dispersion demonstrated antioxidant activity (the ABTS, CUPRAC, DDPH, FRAP assays) and neuroprotective effects by inhibiting acetylcholinesterase and butyrylcholinesterase. FIS modulated gut microbiota, reducing potentially pathogenic gram-negative bacteria without affecting probiotic microflora. These improvements in solubility, antioxidant and neuroprotective activities, and gut microbiome modulation suggest the potential for optimising FIS delivery systems to leverage its health-promoting properties while addressing oral functionality limitations.

Amorphous Solid Dispersion of Hesperidin with Polymer Excipients for Enhanced Apparent Solubility as a More Effective Approach to the Treatment of Civilization Diseases.

The present study reports amorphous solid dispersions (ASDs) of hesperidin (Hes) prepared by ball milling to improve its solubility and apparent solubility over the unmodified compound. The carriers were Soluplus® (Sol), alginate sodium (SA), and hydroxypropylmethylcellulose (HPMC). XRPD analysis confirmed full amorphization of all binary systems in 1:5 w/w ratio. One glass transition (Tg) observed in DSC thermograms of hesperidin:Soluplus® (Hes:Sol) and hesperidin:HPMC (Hes:HPMC) 1:5 w/w systems confirmed complete miscibility. The mathematical model (Gordon-Taylor equation) indicates that the obtained amorphous systems are characterized by weak interactions. The FT-IR results confirmed that hydrogen bonds are responsible for stabilizing the amorphous state of Hes. Stability studies indicate that the strength of these bonds is insufficient to maintain the amorphous state of Hes under stress conditions (25 °C and 60 °C 76.4% RH). HPLC analysis suggested that the absence of degradation products indicates safe hesperidin delivery systems. The solubility and apparent solubility were increased in all media (water, phosphate buffer pH 6.8 and HCl (0.1 N)) compared to the pure compound. Our study showed that all obtained ASDs are promising systems for Hes delivery, wherein Hes:Sol 1:5 w/w has the best solubility (about 300-fold in each media) and apparent solubility (about 70% in phosphate buffer pH 6.8 and 63% in HCl).

Antioxidant Potential of Resveratrol as the Result of Radiation Exposition.

The purpose of this study was to determine the effect of electron beam irradiation (EBI) at a dose of 25 kGy on the stability and antioxidant properties of resveratrol (RSV), a nutraceutical with clinically proven activity. The electron paramagnetic resonance (EPR) method was used to evaluate the concentration of free radicals after irradiation. Minor changes in chemical structure due to free radicals induced by EBI were confirmed by FTIR spectroscopy. HPLC and HPLC-MS analysis ruled out the appearance of degradation products after irradiation. In addition, HPLC analysis confirmed the absence of trans- to cis-resveratrol conversion. Changes in the antioxidant potential of RSV after irradiation were studied using DPPH, ABTS, CUPRAC, and FRAP techniques. It was confirmed that EBI favorably affected the antioxidant properties of tests based on the HAT mechanism (increase in DPPH and CUPRAC tests).

Is Caperatic Acid the Only Compound Responsible for Activity of Lichen Platismatia glauca within the Nervous System?

Lichens are a source of various biologically active compounds. However, the knowledge about them is still scarce, and their use in medicine is limited. This study aimed to investigate the therapeutic potential of the lichen Platismatia glauca and its major metabolite caperatic acid in regard to their potential application in the treatment of central nervous system diseases, especially neurodegenerative diseases and brain tumours, such as glioblastoma. First, we performed the phytochemical analysis of the tested P. glauca extracts based on FT-IR derivative spectroscopic and gas chromatographic results. Next the antioxidant properties were determined, and moderate anti-radical activity, strong chelating properties of Cu2+ and Fe2+ ions, and a mild effect on the antioxidant enzymes of the tested extracts and caperatic acid were proved. Subsequently, the influence of the tested extracts and caperatic acid on cholinergic transmission was determined by in vitro and in silico studies confirming that inhibitory effect on butyrylcholinesterase is stronger than against acetylcholinesterase. We also confirmed the anti-inflammatory properties of P. glauca extracts and caperatic acid using a COX-2 and hyaluronidase inhibition models. Moreover, our studies show the cytotoxic and pro-apoptotic activity of the P. glauca extracts against T98G and U-138 MG glioblastoma multiforme cell lines. In conclusion, it is possible to assume that P. glauca extracts and especially caperatic acid can be regarded as the source of the valuable substances to finding new therapies of central nervous system diseases.

Cyclodextrin Derivatives as Promising Solubilizers to Enhance the Biological Activity of Rosmarinic Acid.

Rosmarinic acid (RA) is a natural antioxidant with neuroprotective properties; however, its preventive and therapeutic use is limited due to its slight solubility and poor permeability. This study aimed to improve RA physicochemical properties by systems formation with cyclodextrins (CDs): hydroxypropyl-α-CD (HP-α-CD), HP-ß-CD, and HP-γ-CD, which were prepared by the solvent evaporation (s.e.) method. The interactions between components were determined by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier Transform infrared spectroscopy (FTIR). The sites of interaction between RA and CDs were suggested as a result of in silico studies focused on assessing the interaction between molecules. The impact of amorphous systems formation on water solubility, dissolution rate, gastrointestinal (GIT) permeability, and biological activity was studied. RA solubility was increased from 5.869 mg/mL to 113.027 mg/mL, 179.840 mg/mL, and 194.354 mg/mL by systems formation with HP-α-CD, HP-ß-CD, and HP-γ-CD, respectively. During apparent solubility studies, the systems provided an acceleration of RA dissolution. Poor RA GIT permeability at pH 4.5 and 5.8, determined by parallel artificial membrane permeability assay (PAMPA system), was increased; RA-HP-γ-CD s.e. indicated the greatest improvement (at pH 4.5 from Papp 6.901 × 10-7 cm/s to 1.085 × 10-6 cm/s and at pH 5.8 from 5.019 × 10-7 cm/s to 9.680 × 10-7 cm/s). Antioxidant activity, which was determined by DPPH, ABTS, CUPRAC, and FRAP methods, was ameliorated by systems; the greatest results were obtained for RA-HP-γ-CD s.e. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) was increased from 36.876% for AChE and 13.68% for BChE to a maximum inhibition of the enzyme (plateau), and enabled reaching IC50 values for both enzymes by all systems. CDs are efficient excipients for improving RA physicochemical and biological properties. HP-γ-CD was the greatest one with potential for future food or dietary supplement applications.

Supercapacitance in graphene oxide materials modified with tetrapyrrole dyes: a mechanistic study.

The global increase in mobile technology usage has created a need for better energy storage systems. With standard batteries reaching their technological limits, alternate energy storage methods are gaining momentum. In this study, we demonstrate a cheap and efficient way of building from scratch high-performance supercapacitors based on graphene oxide (GO) functionalized with tetrapyrrole derivatives: porphyrins and phthalocyanines. We present supercapacitors with capacitances about 30 times larger than those of the pristine graphene oxide-based counterparts. Experimental characterisation methods including X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-VIS), electron paramagnetic resonance (EPR), and density functional theory (DFT) calculations revealed correlations between the structural, magnetic, electronic and thermodynamic properties of these materials and their performance as supercapacitors. Electrochemical studies indicate the complex and versatile nature of capacitive effects associated with thin layers of supramolecular composites of graphene oxide. The electrical double layer (EDL) capacitance, cation intercalation and faradaic processes are coupled. Moreover, differences in the electronic interactions between GO and tetrapyrrolic modifiers have a profound effect on the observed capacitance. At the same time, these interactions are sufficiently weak to induce only subtle spectral changes, as well as a small increase of the interlayer distance as determined by XRD measurements. The present work offers a viable strategy for manufacturing high-performance supercapacitive materials that are superior to the state of the art nanocarbon-based supercapacitors using benign electrolytes in terms of capacitance per mass unit and have the potential for application in future green energy storage technologies. Our study provides insight into the multifarious origins of supercapacitance beyond the well-known EDL mechanism.

Amorphous Inclusion Complexes: Molecular Interactions of Hesperidin and Hesperetin with HP-Β-CD and Their Biological Effects.

This study aimed at obtaining hesperidin (Hed) and hesperetin (Het) systems with HP-ß-CD by means of the solvent evaporation method. The produced systems were identified using infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC). Moreover, in silico docking and molecular dynamics studies were performed to assess the most preferable site of interactions between tested compounds and HP-ß-CD. The changes of physicochemical properties (solubility, dissolution rate, and permeability) were determined chromatographically. The impact of modification on biological activity was tested in an antioxidant study as well as with regards to inhibition of enzymes important in pathogenesis of neurodegenerative diseases. The results indicated improvement in solubility over 1000 and 2000 times for Hed and Het, respectively. Permeability studies revealed that Hed has difficulties in crossing biological membranes, in contrast with Het, which can be considered to be well absorbed. The improved physicochemical properties influenced the biological activity in a positive manner by the increase in inhibitory activity on the DPPH radical and cholinoesterases. To conclude the use of HP-ß-CD as a carrier in the formation of an amorphous inclusion complex seems to be a promising approach to improve the biological activity and bioavailability of Hed and Het.

The Chitosan-Based System with Scutellariae baicalensis radix Extract for the Local Treatment of Vaginal Infections.

Scutellarie baicalensis radix, as a flavone-rich source, exhibits antibacterial, antifungal, antioxidant, and anti-inflammatory activity. It may be used as a therapeutic agent to treat various diseases, including vaginal infections. In this study, six binary mixtures of chitosan with stable S. baicalensis radix lyophilized extract were obtained and identified by spectral (ATR-FTIR, XRPD) and thermal (TG and DSC) methods. The changes in dissolution rates of active compounds and the significant increase in the biological properties towards metal chelating activity were observed, as well as the inhibition of hyaluronic acid degradation after mixing plant extract with chitosan. Moreover, the combination of S. baicalensis radix lyophilized extract with a carrier allowed us to obtain the binary systems with a higher antifungal activity than the pure extract, which may be effective in developing new strategies in the vaginal infections treatment, particularly vulvovaginal candidiasis.

Amorphous Form of Carvedilol Phosphate-The Case of Divergent Properties.

The amorphous form of carvedilol phosphate (CVD) was obtained as a result of grinding. The identity of the obtained amorphous form was confirmed by powder X-ray diffraction (PXRD), different scanning calorimetry (DSC), and FT-IR spectroscopy. The process was optimized in order to obtain the appropriate efficiency and time. The crystalline form of CVD was used as the reference standard. Solid dispersions of crystalline and amorphous CVD forms with hydrophilic polymers (hydroxypropyl-ß-cyclodextrin, Pluronic® F-127, and Soluplus®) were obtained. Their solubility at pH 1.2 and 6.8 was carried out, as well as their permeation through a model system of biological membranes suitable for the gastrointestinal tract (PAMPA-GIT) was established. The influence of selected polymers on CVD properties was defined for the amorphous form regarding the crystalline form of CVD. As a result of grinding (four milling cycles lasting 15 min with 5 min breaks), amorphous CVD was obtained. Its presence was confirmed by the "halo effect" on the diffraction patterns, the disappearance of the peak at 160.5 °C in the thermograms, and the changes in position/disappearance of many characteristic bands on the FT-IR spectra. As a result of changes in the CVD structure, its lower solubility at pH 1.2 and pH 6.8 was noted. While the amorphous dispersions of CVD, especially with Pluronic® F-127, achieved better solubility than combinations of crystalline forms with excipients. Using the PAMPA-GIT model, amorphous CVD was assessed as high permeable (Papp > 1 × 10-6 cm/s), similarly with its amorphous dispersions with excipients (hydroxypropyl-ß-cyclodextrin, Pluronic® F-127, and Soluplus®), although in their cases, the values of apparent constants permeability were decreased.