Publikacje

2025

Abstract

Curcumin, a compound known for its antioxidant and neuroprotective properties, faces challenges due to its low water solubility, which can limit its effectiveness. One effective method to address this issue is through amorphization. Incorporating curcumin into a polymeric matrix to form amorphous solid dispersions is a common approach. Another strategy involves co-amorphous systems, where low-molecular-weight components act as co-formers. A recent innovative approach combines these strategies. This study used tryptophan as a co-former and prepared systems using supercritical fluid technology. The amorphous nature of two systems was confirmed through X-ray powder diffraction: one with 10% curcumin and a polymer, and another with 10% curcumin, a polymer, and tryptophan. Fourier-transform infrared analysis demonstrated molecular interactions among all components in the systems. Scanning electron microscopy revealed that the amorphization process significantly modified the morphology of the powder particles. The ternary system with tryptophan notably increased curcumin solubility by over 300-fold. The amorphous form of curcumin in both systems exhibited significantly higher dissolution rates compared to its crystalline form. The system with tryptophan showed more than a threefold improvement in permeability according to the PAMPA test. The enhanced solubility led to over a sixfold increase in antioxidant activity and a 25-fold improvement in the inhibition of the enzyme butyrylcholinesterase.

Keywords: curcumin; amorphous; tryptophan; supercritical fluid technology

Abstract

Apigenin (APG), a bioactive flavonoid with promising therapeutic potential, suffers from poor water solubility, which limits its bioavailability. To address this, solid dispersions of APG were prepared using ball milling with sodium alginate (SA), Pluronic® F-68 (PLU68), Pluronic® F-127 (PLU127), PVP K30, and PVP VA64 as polymeric excipients. These dispersions were screened for apparent solubility in water and buffers with pH 1.2, 5.5, and 6.8. Based on improved solubility after 60 min, APG–PLU68 and APG–PLU127 dispersions were selected for further study. DSC and FT-IR analysis confirmed molecular interactions between APG and the polymer matrices, contributing to enhanced solubility and dissolution rates. Dissolution rate studies showed that APG–PLU127 achieved 100% solubility at pH 6.8, suggesting its potential use in environments such as the small intestine. Additionally, APG–PLU127 exhibited 84.3% solubility at pH 1.2, indicating potential for solid oral dosage forms, where APG could be absorbed in the acidic conditions of the stomach. The stability study confirmed that storage for one year under ambient conditions does not cause chemical degradation but affects the physical state and solubility of the dispersion. Antioxidant activity was assessed using the ABTS assay. Freshly obtained APG–PLU127 showed 68.1% ± 1.94% activity, whereas APG–PLU127 stored for one year under ambient conditions exhibited 66.2% ± 1.62% (significant difference, p < 0.05). The difference was related to a slight decrease in the solubility of APG in the solid dispersion (T0 = 252 ± 1 μg∙mL−1, T1 = 246 ± 1 μg∙mL−1). The findings demonstrate the superior performance of PLU127 as a carrier for enhancing the solubility, release, and antioxidant activity of APG. 

Abstract

Background: Curcumin and hesperetin are plant polyphenols known for their poor solubility. To address this limitation, we prepared amorphous PVP K30–phosphatidylcholine dispersions via hot-melt extrusion. Methods: This study aimed to evaluate the effects of the amounts of active ingredients and phosphatidylcholine, as well as the process temperature, on the performance of the dispersions. A Box–Behnken design was employed to assess these factors. Solid-state characterization and biopharmaceutical studies were then conducted. X-ray powder diffraction (XRPD) was used to confirm the amorphous nature of the dispersions, while differential scanning calorimetry (DSC) provided insight into the miscibility of the systems. Fourier-transform infrared spectroscopy (FTIR) was employed to assess the intermolecular interactions. The apparent solubility and dissolution profiles of the systems were studied in phosphate buffer at pH 6.8. In vitro permeability across the gastrointestinal tract and blood–brain barrier was evaluated using the parallel artificial membrane permeability assay. 

Results: The quantities of polyphenols and phospholipids were identified as significant factors influencing the biopharmaceutical performance of the systems. Solid-state analysis confirmed the formation of amorphous dispersions and the development of interactions among components. Notably, a significant improvement in solubility was observed, with formulations exhibiting distinct release patterns for the active compounds. Furthermore, the in vitro permeability through the gastrointestinal tract and blood–brain barrier was enhanced. 

Conclusions: The findings suggest that amorphous PVP K30–phosphatidylcholine dispersions have the potential to improve the biopharmaceutical properties of curcumin and hesperetin.

2024

Abstract

Curcumin and piperine are plant compounds known for their health-promoting properties, but their use in the prevention or treatment of various diseases is limited by their poor solubility. To overcome this drawback, the curcumin–piperine amorphous polymer–phospholipid dispersions were prepared by hot melt extrusion technology. X-ray powder diffraction indicated the formation of amorphous systems. Differential scanning calorimetry confirmed amorphization and provided information on the good miscibility of the active compound–polymer–phospholipid dispersions. Owing to Fourier-transform infrared spectroscopy, the intermolecular interactions in systems were investigated. In the biopharmaceutical properties assessment, the improvement in solubility as well as the maintenance of the supersaturation state were confirmed. Moreover, PAMPA models simulating the gastrointestinal tract and blood-brain barrier showed enhanced permeability of active compounds presented in dispersions compared to the crystalline form of individual compounds. The presented paper suggests that polymer–phospholipid dispersions advantageously impact the bioaccessibility of poorly soluble active compounds. 

Abstract

The co-administration of curcumin and hesperetin might be beneficial in terms of neuroprotective activity; therefore, in this study, we attempted to develop a fixed-dose formulation comprising these two compounds in an amorphous state. The aim of obtaining an amorphous state was to overcome the limitations of the low solubility of the active compounds. First, we assessed the possibility of using popular sweeteners (erythritol, xylitol, and sorbitol) as plasticizers to reduce the glass transition temperature of PVP K30 to prepare the polymer–excipient blends, which allowed the preparation of amorphous solid dispersions via hot-melt extrusion at a temperature below the original glass transition of PVP K30. Erythritol proved to be the superior plasticizer. Then, we focused on the development of fixed-dose amorphous solid dispersions of curcumin and hesperetin. Powder X-ray diffraction and thermal analysis confirmed the amorphous character of dispersions, whereas infrared spectroscopy helped to assess the presence of intermolecular interactions. The amorphous state of the produced dispersions was maintained for 6 months, as shown in a stability study. Pharmaceutical parameters such as dissolution rate, solubility, and in vitro permeability through artificial membranes were evaluated. The best improvement in these features was noted for the dispersion, which contained 15% of the total content of the active compounds with erythritol used as the plasticizer. 

Abstract

In this study, binary amorphous solid dispersions (ASDs, fisetin-Eudragit®) and ternary amorphous solid inclusions (ASIs, fisetin-Eudragit®-HP-β-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-β-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%). 

Abstract

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. 

Abstract

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. 

2023

Abstract

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. 

Abstract

As secondary plant metabolites, polyphenols are abundant in fruits and vegetables. They are in high demand because of their many health benefits. However, their low bioavailability makes them complex compounds to use for therapeutic purposes. Due to the limited solubility of phytocompounds, dietary supplements made from them may only be partially effective. Such molecules include fisetin, found in strawberries, and have shown great promise in treating Alzheimer’s disease and cancer. Unfortunately, because of their limited water solubility, low absorption, and poor bioavailability, the assistance of nanotechnology is required to allow them to fulfil their potential fully. Here, we provide evidence that nanodelivery methods and structure modifications can improve fisetin bioavailability, which is linked to improvements in therapeutic efficacy. An open question remains as to which nanocarrier should be chosen to meet the abovementioned requirements and be able to enhance fisetin’s therapeutic potential to treat a particular disease. 

Abstract

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. 

Abstract

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. 

Abstract

Hesperidin is a polyphenol derived from citrus fruits that has a broad potential for biological activity and the ability to positively modify the intestinal microbiome. However, its activity is limited by its low solubility and, thus, its bioavailability—this research aimed to develop a zein-based hesperidin system with increased solubility and a sustained release profile. The study used triple systems enriched with solubilizers to maximize solubility. The best system was the triple system hesperidin-zein-Hpβ-CD, for which the solubility improved by more than six times. A significant improvement in the antioxidant activity and the ability to inhibit α-glucosidase was also demonstrated, due to an improved solubility. A release profile analysis was performed in the subsequent part of the experiments, confirming the sustained release profile of hesperidin, while improving the solubility. Moreover, the ability of selected probiotic bacteria to metabolize hesperidin and the effect of this flavonoid compound on their growth were investigated. 

Abstract

The low bioaccessibility of hesperetin and piperine hampers their application as therapeutic agents. Piperine has the ability to improve the bioavailability of many compounds when co-administered. The aim of this paper was to prepare and characterize the amorphous dispersions of hesperetin and piperine, which could help to improve solubility and boost the bioavailability of both plant-origin active compounds. The amorphous systems were successfully obtained by means of ball milling, as confirmed by XRPD and DSC studies. What’s more, the FT-IR-ATR study was used to investigate the presence of intermolecular interactions between the systems’ components. Amorphization enhanced the dissolution rate as a supersaturation state was reached, as well as improving the apparent solubility of both compounds by 245-fold and 183-fold, respectively, for hesperetin and piperine. In the in vitro permeability studies simulating gastrointestinal tract and blood-brain barrier permeabilities, these increased by 775-fold and 257-fold for hesperetin, whereas they were 68-fold and 66-fold for piperine in the GIT and BBB PAMPA models, respectively. Enhanced solubility had an advantageous impact on antioxidant as well as anti-butyrylcholinesterase activities—the best system inhibited 90.62 ± 0.58% of DPPH radicals and 87.57 ± 1.02% butyrylcholinesterase activity. To sum up, amorphization considerably improved the dissolution rate, apparent solubility, permeability, and biological activities of hesperetin and piperine. 

Abstract

Poor bioavailability hampers the use of curcumin and piperine as biologically active agents. It can be improved by enhancing the solubility as well as by using bioenhancers to inhibit metabolic transformation processes. Obtaining an amorphous system of curcumin and piperine can lead to the overcoming of these limitations. Hot-melt extrusion successfully produced their amorphous systems, as shown by XRPD and DSC analyses. Additionally, the presence of intermolecular interactions between the components of the systems was investigated using the FT-IR/ATR technique. The systems were able to produce a supersaturation state as well as improve the apparent solubilities of curcumin and piperine by 9496- and 161-fold, respectively. The permeabilities of curcumin in the GIT and BBB PAMPA models increased by 12578- and 3069-fold, respectively, whereas piperine’s were raised by 343- and 164-fold, respectively. Improved solubility had a positive effect on both antioxidant and anti-butyrylcholinesterase activities. The best system suppressed 96.97 ± 1.32% of DPPH radicals, and butyrylcholinesterase activity was inhibited by 98.52 ± 0.87%. In conclusion, amorphization remarkably increased the dissolution rate, apparent solubility, permeability, and biological activities of curcumin and piperine. 

Abstract

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. 

Abstract

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). 

2022

Abstract

The presented research evaluates the medical use potential of Lonicera caerulea leaves, which are waste plants in cultivating berries. The study’s screening activity included the leaves of five varieties of Lonicera caerulea: Atut, Duet, Wojtek, Zojka, and Jugana. The microbiological analysis confirmed the safety of using Lonicera caerulea leaves without significant stabilization. Lonicera caerulea leaves standardization was carried out based on the results of the chromatographic analysis, and it showed differences in the contents of active compounds (loganic, chlorogenic and caffeic acids, and rutin), which are attributed to biological activity. For the Lonicera caerulea leaves varieties tested, the differences in the content of total polyphenol content, chlorophylls, and carotenoids were also confirmed. The screening of biological activity of five Lonicera caerulea leaf varieties was carried out concerning the possibility of inhibiting the activity of α-glucosidase, lipase, and hyaluronidase as well, and the antioxidant potential was determined. The defined profile of the biological activity of Lonicera caerulea leaves makes it possible to indicate this raw material as an essential material supporting the prevention and treatment of type II diabetes. However, this research showed that tested enzymes were strongly inhibited by the variety Jugana. The health-promoting potential of Lonicera caerulea leaves was correlated with the highest chlorogenic acid and rutin content in the variety Jugana. 

Abstract

Hesperidin and hesperetin are polyphenols that can be found predominantly in citrus fruits. They possess a variety of pharmacological properties such as neuroprotective and antidiabetic activity. However, the bioavailability of these compounds is limited due to low solubility and restricts their use as pro-healthy agents. This paper described the limitations resulting from the low bioavailability of the presented compounds and gathered the methods aiming at its improvement. Moreover, this work reviewed studies providing pieces of evidence for neuroprotective and antidiabetic properties of hesperidin and hesperetin as well as providing a detailed look into the significance of reported modes of action in chronic diseases. On account of a well-documented pro-healthy activity, it is important to look for ways to overcome the problem of poor bioavailability. 

Abstract

As a systemic disease, diabetes mellitus (DM) is characterized by the disruption of many glucose metabolic pathways. Therefore, it seems critical to study new therapies to support treatment to develop therapeutic systems that can operate across a broad metabolic spectrum. The current state of knowledge indicates an essential role of the gut microbiota in the development and course of the disease. Cornus mas fruits have demonstrated a rich biological activity profile and potential for application in the treatment of DM. As part of a preliminary analysis, the activity of four cultivars of Cornus mas fruits was analyzed. The cultivar Wydubieckij was selected as having the highest activity in in vitro conditions for further prebiotic system preparation. The study aimed to develop a unique therapeutic system based, first of all, on the mechanism of α-glucosidase inhibition and the antioxidant effect resulting from the activity of the plant extract used, combined with the prebiotic effect of inulin. The obtained system was characterized in vitro in terms of antioxidant activity and enzyme inhibition capacity, and was then tested on diabetic rats. The study was coupled with an analysis of changes in the intestinal microflora. The system of prebiotic stabilized Cornus mas L. lyophilized extract with inulin offers valuable support for the prophylaxis and treatment of DM. 

Abstract

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). 

Abstract

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-β-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-β-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. 

Abstract

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. 

Abstract

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). 

Abstract

As a systemic disease, diabetes mellitus (DM) is characterized by the disruption of many glucose metabolic pathways. Therefore, it seems critical to study new therapies to support treatment to develop therapeutic systems that can operate across a broad metabolic spectrum. The current state of knowledge indicates an essential role of the gut microbiota in the development and course of the disease. Cornus mas fruits have demonstrated a rich biological activity profile and potential for application in the treatment of DM. As part of a preliminary analysis, the activity of four cultivars of Cornus mas fruits was analyzed. The cultivar Wydubieckij was selected as having the highest activity in in vitro conditions for further prebiotic system preparation. The study aimed to develop a unique therapeutic system based, first of all, on the mechanism of α-glucosidase inhibition and the antioxidant effect resulting from the activity of the plant extract used, combined with the prebiotic effect of inulin. The obtained system was characterized in vitro in terms of antioxidant activity and enzyme inhibition capacity, and was then tested on diabetic rats. The study was coupled with an analysis of changes in the intestinal microflora. The system of prebiotic stabilized Cornus mas L. lyophilized extract with inulin offers valuable support for the prophylaxis and treatment of DM. 

Abstract

Nowadays, increasingly more attention is being paid to a holistic approach to health, in which diet contributes to disease prevention. There is growing interest in functional food that not only provides basic nutrition but has also been demonstrated to be an opportunity for the prevention of disorders. A promising functional food is soybean, which is the richest source of the isoflavone, genistein. Genistein may be useful in the prevention and treatment of such disorders as psoriasis, cataracts, cystic fibrosis, non-alcoholic fatty liver disease and type 2 diabetes. However, achievable concentrations of genistein in humans are low, and the use of soybean as a functional food is not devoid of concerns, which are related to genistein’s potential side effects resulting from its estrogenic and goitrogenic effects. 

Abstract

This study aimed at obtaining hesperidin (Hed) and hesperetin (Het) systems with HP-β-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-β-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-β-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. 

2021

Abstract

Piperine is an alkaloid that has extensive pharmacological activity and impacts other active substances bioavailability due to inhibition of CYP450 enzymes, stimulation of amino acid transporters and P-glycoprotein inhibition. Low solubility and the associated low bioavailability of piperine limit its potential. The combination of piperine with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) causes a significant increase in its solubility and, consequently, an increase in permeability through gastrointestinal tract membranes and the blood–brain barrier. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) were used to characterize interactions between piperine and HP-β-CD. The observed physicochemical changes should be combined with the process of piperine and CD system formation. Importantly, with an increase in solubility and permeability of piperine as a result of interaction with CD, it was proven to maintain its biological activity concerning the antioxidant potential (2,2-diphenyl-1-picryl-hydrazyl-hydrate assay), inhibition of enzymes essential for the inflammatory process and for neurodegenerative changes (hyaluronidase, acetylcholinesterase, butyrylcholinesterase). 

Abstract

Lichen secondary metabolites are characterized by huge pharmacological potential. Our research focused on assessing the anticancer and neuroprotective activity of Hypogymnia physodes acetone extract (HP extract) and physodic acid, its major component. The antitumor properties were evaluated by cytotoxicity analysis using A-172, T98G, and U-138 MG glioblastoma cell lines and by hyaluronidase and cyclooxygenase-2 (COX-2) inhibition. The neuroprotective potential was examined using COX-2, tyrosinase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) activity tests. Moreover, the antioxidant potential of the tested substances was examined, and the chemical composition of the extract was analyzed. For physodic acid, the permeability through the blood–brain barrier using Parallel Artificial Membrane Permeability Assay for the Blood–Brain Barrier assay (PAMPA-BBB) was assessed. Our study shows that the tested substances strongly inhibited glioblastoma cell proliferation and hyaluronidase activity. Besides, HP extract diminished COX-2 and tyrosinase activity. However, the AChE and BChE inhibitory activity of HP extract and physodic acid were mild. The examined substances exhibited strong antioxidant activity. Importantly, we proved that physodic acid crosses the blood–brain barrier. We conclude that physodic acid and H. physodes should be regarded as promising agents with anticancer, chemopreventive, and neuroprotective activities, especially regarding the central nervous system diseases. 

Abstract

Bearing in mind the growing interest in Yerba Mate, a comprehensive study has been prepared containing the most important aspects and possibilities of its use. The introduction of the work contains the species characteristics of Yerba Mate, as well as information about the origin and places of cultivation. The next part focuses on the analysis of the composition, pointing to purine alkaloids, polyphenols, saponins, and minerals as groups of active compounds responsible for the clinical activity of Yerba Mate. The review of the results of preclinical and clinical studies indicates activity in relation to the stimulating effect, reducing weight by stimulating lipolysis, cardioprotective, anti-diabetic, and anti-inflammatory effects. The information about the action of Yerba Mate is supplemented by the characteristics of its potential toxicity in terms of PAHs content (in particular benzo[α]pyrene) and preparation as a determinant of increased irritation. The current data on the effects of Yerba Mate and the wide safety margin of its use position this raw material as a valuable component of functional food. The growing frequency of consuming Yerba Mate, conditioned by the availability resulting from the globalization of the market and the information provided about it’s the pro-health effects, will position Yerba Mate’s popularity among wider population groups.