Investigating the Wound-Healing Potential of a Nanoemulsion-Gel Formulation of Pituranthos tortuosus Essential Oil.

This study explores a nanoemulsion (NE)-based gel incorporating Tunisian Pituranthos tortuosus essential oil, with a focus on its wound-healing potential. The essential oil, extracted via hydrodistillation, underwent GC-MS analysis for compositional verification. The physicochemical characterization included dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential measurement, pH, and viscosity. The gelification of the NE facilitated topical application. The results revealed an average extraction yield of 0.45% and identified 38 compounds in the essential oil. The NE exhibited a particle size of 27 ± 0.4 nm, a polydispersity index (PDI) of 0.3, and a zeta potential of -22.8 ± 1.4 mV. The stability of the gelified preparation was confirmed through thermodynamic stability studies, TEM observations, and zeta and size results. In vivo experiments confirmed significant wound-healing effects, highlighting the promising role of the NE-based gel in healthcare advancements. This research underscores the potential of novel phyto-based delivery systems in wound care.

Exploring the chemical and pharmacological variability of Lepidium meyenii: a comprehensive review of the effects of maca.

Maca (Lepidium meyenii), a biennial herbaceous plant indigenous to the Andes Mountains, has a rich history of traditional use for its purported health benefits. Maca's chemical composition varies due to ecotypes, growth conditions, and post-harvest processing, contributing to its intricate phytochemical profile, including, macamides, macaenes, and glucosinolates, among other components. This review provides an in-depth revision and analysis of Maca's diverse bioactive metabolites, focusing on the pharmacological properties registered in pre-clinical and clinical studies. Maca is generally safe, with rare adverse effects, supported by preclinical studies revealing low toxicity and good human tolerance. Preclinical investigations highlight the benefits attributed to Maca compounds, including neuroprotection, anti-inflammatory properties, immunoregulation, and antioxidant effects. Maca has also shown potential for enhancing fertility, combating fatigue, and exhibiting potential antitumor properties. Maca's versatility extends to metabolic regulation, gastrointestinal health, cardio protection, antihypertensive activity, photoprotection, muscle growth, hepatoprotection, proangiogenic effects, antithrombotic properties, and antiallergic activity. Clinical studies, primarily focused on sexual health, indicate improved sexual desire, erectile function, and subjective wellbeing in men. Maca also shows promise in alleviating menopausal symptoms in women and enhancing physical performance. Further research is essential to uncover the mechanisms and clinical applications of Maca's unique bioactive metabolites, solidifying its place as a subject of growing scientific interest.

Accelerated Cr (VI) removal by a three-dimensional electro-Fenton system using green iron nanoparticles.

Green-synthesized iron nanoparticles (GAP-FeNP) were used as particle electrodes in a three-dimensional electro-Fenton (3DEF) process to accelerate the removal of hexavalent chromium [Cr (VI)]. Removal was evaluated by varying the pH (3.0, 6.0, and 9.0) and initial Cr (VI) concentrations (10, 30, and 50 mg/L) at 5 and 25 min. These results demonstrated that GAP-FeNP/3DEF treatment achieved more than 94% Cr (VI) removal under all tested conditions. Furthermore, it was observed that Cr (VI) removal exceeded 98% under pH 9.0 in all experimental parameters tested. The results of the response surface methodology (RSM) determined two optimal conditions: the first, characterized by a pH of 3.0, Cr (VI) concentration at 50 mg/L, and 25 min, yielded a Cr (VI) removal of 99.7%. The second optimal condition emerged at pH 9.0, with Cr (VI) concentrations of 10 mg/L and 5 min, achieving a Cr (VI) removal of 99.5%. This study highlights the potential of the GAP-FeNP to synergistically accelerate Cr (VI) removal by the 3DEF process, allowing faster elimination and expansion of the alkaline (pH 9.0) applicability. PRACTITIONER POINTS: The required time for >99% of Cr (VI) removal by the GAP-FeNP/3DEF process was shortened from 25 to 5 min. EF process with GAP-FeNP reduces the time necessary for Cr (VI) removal, which is 67% faster than conventional methods. EF process using GAP-FeNP removed >94% of Cr (VI) after 25 min for all initial Cr (VI) concentrations and pH treatments. Cr (VI) removal by the GAP-FeNP/3DEF process was >98% at a pH of 9.0, widening the solution pH applicability.

Physico-Chemical comparison of four commercially available mineral trioxide aggregates / Comparación fisicoquímica de cuatro mineral trióxido agregados disponibles comercialmente

Abstract To compare the physicochemical composition of 4 MTAs commercially available in Latin America. ProRoot MTA (Dentsply, USA), MTA Angelus (Angelus, Brazil), MTA Flow (Ultradent, USA), and MTA Viarden (Viarden, Mexico) were physically and chemically compared. Scanning electron microscopy (SEM) images were obtained from the MTA powder and the prepared presentations. Energy Dispersive X-Ray Spectroscopy (EDS) analyses were performed by triplicate, to calculate the mass proportion of calcium (Ca), silicon (Si), the Ca/Si proportion among the 4 brands. Thermogravimetric analyses (TGA) were conducted (50ºC-1000ºC), and mass loss and inflection points were calculated for each material. Statistical differences for Ca and Si content were determined by ANOVA (p<0.05). SEM images showed evident differences in the appearance of both the powder and the prepared MTAs among brands. Angelus MTA showed cubic prisms not observed in the other 3 brands. ProRoot MTA and MTA Flow showed similar homogeneous structures. MTA Viarden was the less homogeneous, with random structures (>15um). When comparing the mass proportions of Ca and Si between the 4 powder samples, MTA Viarden showed a significantly lower proportions of both elements when compared with the other brands (p<0.005). TGA análisis showed a similar behavior for ProRoot MTA, MTA Angelus and MTA Flow, with less than 2% mass loss when the 1000C temperature was reached. MTA Viarden showed a mass loss of 9,94% before the 700C, indicating the presence of different content sensible to temperature degradation. The analyzed MTAs demonstrated to vary significantly in their chemical composition and physical characteristics. Clinicians must be aware of the differences between different brands of a same material, and future research should focus on the clinical implications of these differences.

Resumen Comparar la composición fisicoquímica de 4 MTA disponibles comercialmente en América Latina. Se compararon física y químicamente ProRoot MTA (Dentsply, EE. UU.), MTA Angelus (Angelus, Brasil), MTA Flow (Ultradent, EE. UU.) y MTA Viarden (Viarden, México). Se obtuvieron imágenes de microscopía electrónica de barrido (SEM) del polvo de MTA y de las presentaciones preparadas. Los análisis de espectroscopía de dispersión de energía de rayos X (EDS) se realizaron por triplicado para calcular la proporción de masa de calcio (Ca), silicio (Si), la proporción Ca/Si entre las 4 marcas. Se realizaron análisis termogravimétricos (TGA) (50ºC-1000ºC), y se calcularon las pérdidas de masa y los puntos de inflexión para cada material. Las diferencias estadísticas para el contenido de Ca y Si se determinaron mediante ANOVA (p<0,05). Los análisis SEM mostraron diferencias evidentes en la apariencia tanto del polvo como las preparaciones de los MTA, entre las diferentes marcas. MTA Angelus mostró prismas cúbicos no observados en las otras 3 marcas. ProRoot MTA y MTA Flow mostraron estructuras homogéneas similares. MTA Viarden fue el menos homogéneo, con estructuras aleatorias (>15um). Al comparar las proporciones de masa de Ca y Si entre las 4 muestras de polvo, MTA Viarden mostró proporciones significativamente más bajas de ambos elementos en comparación con las otras marcas (p<0,005). El análisis TGA mostró un comportamiento similar para ProRoot MTA, MTA Angelus y MTA Flow, con menos del 2 % de pérdida de masa al alcanzar los 1000 °C de temperatura. El MTA Viarden mostró una pérdida de masa de 9,94% antes de los 700 °C, indicando la presencia de diferentes contenidos sensibles a la degradación por temperatura. Los MTA analizados demostraron diferencias significativas en su composición química y características físicas. Los clínicos deben ser conscientes de las diferencias entre las diferentes marcas de un mismo material, y futuras investigaciones deben enfocarse en las implicaciones clínicas de estas diferencias.

Sphingolipid-Based Synergistic Interactions to Enhance Chemosensitivity in Lung Cancer Cells.

Tumor heterogeneity leads to drug resistance in cancer treatment with the crucial role of sphingolipids in cell fate and stress signaling. We analyzed sphingolipid metabolism and autophagic flux to study chemotherapeutic interactions on the A549 lung cancer model. Loaded cells with fluorescent sphingomyelin analog (BODIPY) and mCherry-EGFP-LC3B were used to track autophagic flux and assess cytotoxicity when cells are exposed to chemotherapy (epirubicin, cisplatin, and paclitaxel) together with sphingolipid pathway inhibitors and autophagy modulators. Our cell model approach employed fluorescent sphingolipid biosensors and a Gaussian Mixture Model of cell heterogeneity profiles to map the influence of chemotherapy on the sphingolipid pathway and infer potential synergistic interactions. Results showed significant synergy, especially when combining epirubicin with autophagy inducers (rapamycin and Torin), reducing cell viability. Cisplatin also synergized with a ceramidase inhibitor. However, paclitaxel often led to antagonistic effects. Our mapping model suggests that combining chemotherapies with autophagy inducers increases vesicle formation, possibly linked to ceramide accumulation, triggering cell death. However, the in silico model proposed ceramide accumulation in autophagosomes, and kinetic analysis provided evidence of sphingolipid colocalization in autophagosomes. Further research is needed to identify specific sphingolipids accumulating in autophagosomes. These findings offer insights into potential strategies for overcoming chemotherapy resistance by targeting the sphingolipid pathway.

Optimization of the biosynthesis of silver nanoparticles using bacterial extracts and their antimicrobial potential.

In the present study, silver nanoparticles (AgNPs) were biosynthesized using the supernatant and the intracellular extract of Cupriavidus necator, Bacillus megaterium, and Bacillus subtilis. The characterization of the AgNPs was carried out using UV-Vis spectroscopy, FTIR, DLS and TEM. Resazurin microtiter-plate assay was used to determine the antimicrobial action of AgNPs against Escherichia coli. UV-Visible spectra showed peaks between 414 and 460 nm. TEM analysis revealed that the synthesized AgNPs showed mostly spherical shapes. DLS results determined sizes from 20.8 to 118.4 nm. The highest antimicrobial activity was obtained with the AgNPs synthesized with supernatant rather than those using the intracellular extract. Therefore, it was determined that the bacterial species, temperature, pH, and type of extract (supernatant or intracellular) influence the biosynthesis. This synthesis thus offers a simple, environmentally friendly, and low-cost method for the production of AgNPs, which can be used as antibacterial agents.

Saquinavir-Piperine Eutectic Mixture: Preparation, Characterization, and Dissolution Profile.

The dissolution rate of the anti-HIV drug saquinavir base (SQV), a poorly water-soluble and extremely low absolute bioavailability drug, was improved through a eutectic mixture formation approach. A screening based on a liquid-assisted grinding technique was performed using a 1:1 molar ratio of the drug and the coformers sodium saccharinate, theobromine, nicotinic acid, nicotinamide, vanillin, vanillic acid, and piperine (PIP), followed by differential scanning calorimetry (DSC). Given that SQV-PIP was the only resulting eutectic system from the screening, both the binary phase and the Tammann diagrams were adapted to this system using DSC data of mixtures prepared from 0.1 to 1.0 molar ratios in order to determine the exact eutectic composition. The SQV-PIP system formed a eutectic at a composition of 0.6 and 0.40, respectively. Then, a solid-state characterization through DSC, powder X-ray diffraction (PXRD), including small-angle X-ray scattering (SAXS) measurements to explore the small-angle region in detail, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and a powder dissolution test were performed. The conventional PXRD analyses suggested that the eutectic mixture did not exhibit structural changes; however, the small-angle region explored through the SAXS instrument revealed a change in the crystal structure of one of their components. FT-IR spectra showed no molecular interaction in the solid state. Finally, the dissolution profile of SQV in the eutectic mixture was different from the dissolution of pure SQV. After 45 min, approximately 55% of the drug in the eutectic mixture was dissolved, while, for pure SQV, 42% dissolved within this time. Hence, this study concludes that the dissolution rate of SQV can be effectively improved through the approach of using PIP as a coformer.

Evaluation of dentin microroughness and composite bond strength after multiple uses of diamond burs / Evaluación de la micro rugosidad dentinaria y la resistencia adhesiva de composites tras múltiples usos de fresas de diamante

Abstract Using a bur multiple times to prepare dental structure may produce a smoother final surface on dentin than a new one. This superficial roughness may affect adhesion with resin-based materials by modifying the substrates' characteristics. The aim of this study was to evaluate the effect of multiple uses of diamond burs on dentin's superficial microroughness and bond strength with resin composite when using a self-etch adhesive. Diamond dental burs were used to simulate a preparation (dentin flat surface) on extracted third molars. Samples were distributed into groups according to burs' number of previous uses as follows: 0, 1, 5 and 10. Scanning electron microscopy images at 70x, 350x, and 1000x were used to illustrate burs' deformation. Each specimen's dentin microroughness was measured three times to compare between experimental groups and the micro-shear bond strength test (n=15) was performed for the 0 and 10 uses groups using a universal adhesive in a self- etching mode. Diamond crystals wear and dislodgements were evident among groups where the burs were used more times. As the number of uses increased the mean microroughness of the dentin surface decreased with significant differences between the 0 and 10 uses groups. No statistical differences between experimental groups resulted from bond strength tests. When using a universal adhesive in a self-etching mode, the number of previous uses of a diamond bur seems to have no significant effect on dentin/resin composite bond strength.

Resumen El uso de una fresa múltiples veces para preparar la estructura dental puede producir una superficie final más lisa en la dentina que una fresa nueva. Esta rugosidad superficial modifica las características del sustrato y puede afectar la adhesión con materiales resinosos. El objetivo de este estudio fue evaluar el efecto de los múltiples usos de las fresas de diamante sobre la micro rugosidad superficial de la dentina y la resistencia adhesiva con la resina compuesta cuando se utiliza un adhesivo de autograbado. Se utilizaron fresas dentales de diamante para simular una preparación (superficie plana de la dentina) en terceros molares extraídos. Las muestras se distribuyeron en grupos según el número de usos previos de las fresas de la siguiente manera: 0, 1, 5 y 10. Se utilizaron imágenes de microscopía electrónica de barrido a ×70, ×350 y ×1000 para ilustrar la deformación de las fresas. Se midió la micro rugosidad de la dentina de cada espécimen tres veces para comparar entre los grupos experimentales y se realizó la prueba de resistencia a la adhesión por micro cizallamiento (n=15) para los grupos de 0 y 10 usos utilizando un adhesivo universal en modo de autograbado. El desgaste de los cristales de diamante y los desprendimientos fueron evidentes entre los grupos en los que las fresas se utilizaron más veces. A medida que aumentaba el número de usos, la micro rugosidad media de la superficie de la dentina disminuyó, con diferencias significativas entre los grupos de 0 y 10 usos. En las pruebas de resistencia adhesiva no se observaron diferencias estadísticas entre los grupos experimentales. Cuando se utiliza un adhesivo universal en modo de autograbado, el número de usos previos de una fresa de diamante no parece tener un efecto significativo en la resistencia de la unión dentina/resina del composite.

Pineapple Agro-Industrial Biomass to Produce Biomedical Applications in a Circular Economy Context in Costa Rica.

Pineapple is a highly demanded fruit in international markets due to its unique appearance and flavor, high fiber content, vitamins, folic acid, and minerals. It makes pineapple production and processing a significant source of income for producing countries, such as Costa Rica. This review collects bibliographic information dating back to the beginnings of pineapple production in Costa Rica to the state of the market today. It details the impacts of its production chain and proposes a biorefinery as a solution to environmental problems. Besides the potentiality of new sustainable markets to contribute to the post-COVID-19 economy in Costa Rica is highlighted. The general characteristics of pineapple by-products -cellulose, hemicellulose, lignin, and other high-value products like bromelain y saponin- are described, as well as the primary processes for their ex-traction via biorefinery and main applications in the medical field. Finally, a brief description of the main works in the literature involving modeling and simulation studies of pineapple by-products properties is included.

Encapsulated salts in velvet worm slime drive its hardening.

Slime expelled by velvet worms entraps prey insects within seconds in a hardened biopolymer network that matches the mechanical strength of industrial polymers. While the mechanic stimuli-responsive nature and building blocks of the polymerization are known, it is still unclear how the velvet worms' slime hardens so fast. Here, we investigated the slime for the first time, not only after, but also before expulsion. Further, we investigated the slime's micro- and nanostructures in-depth. Besides the previously reported protein nanoglobules, carbohydrates, and lipids, we discovered abundant encapsulated phosphate and carbonate salts. We also detected CO2 bubbles during the hardening of the slime. These findings, along with further observations, suggest that the encapsulated salts in expelled slime rapidly dissolve and neutralize in a baking-powder-like reaction, which seems to accelerate the drying of the slime. The proteins' conformation and aggregation are thus influenced by shear stress and the salts' neutralization reaction, increasing the slime's pH and ionic strength. These insights into the drying process of the velvet worm's slime demonstrate how naturally evolved polymerizations can unwind in seconds, and could inspire new polymers that are stimuli-responsive or fast-drying under ambient conditions.

Curcumin Hybrid Lipid Polymeric Nanoparticles: Antioxidant Activity, Immune Cellular Response, and Cytotoxicity Evaluation.

Poor solubility and short biological half-life present a challenge that needs to be overcome in order to improve the recognized bioactivities of curcumin (CUR), the main phenolic compounds derived from the roots of Curcuma longa. However, drug delivery systems have proven to be an excellent strategy to improve and obtain greater bioavailability. Our previous studies on curcuminoid hybrid nanoparticles have shown promising results by significantly increasing the solubility of desmethoxycurcumin (DMC) and bisdemethoxycurcumin (BDM). In this contribution, we performed a detailed characterization of a CUR as well as in vitro and in vivo studies. The developed method produced CUR loaded nanoparticles with an average size of 49.46 ± 0.80. Moreover, the FT-IR analysis confirmed the encapsulation, and TEM images showed their spherical shape. The NP achieved an encapsulation efficiency greater than 99%. Further, the release studies found that the NPs obtained a significantly higher release than the pure compounds in water. In vivo delayed-type hypersensitivity (DTH) studies showed promising results by enhancing the immune activity response of CUR in NP compared to bulk CUR. Furthermore, we report a significant increase in antioxidant activity for CUR-NP in aqueous solution compared to free CUR. Finally, an important in vitro cytotoxic effect on gastric AGS and colon SW620 adenocarcinoma cell lines was found for CUR-NP while empty carrier nanoparticles are observed to exhibit low cytotoxicity, indicating the potential of these CUR-PLU NPs for further studies to assess their phytotherapeutic applications.

Hybrid Nanoparticles of Proanthocyanidins from Uncaria tomentosa Leaves: QTOF-ESI MS Characterization, Antioxidant Activity and Immune Cellular Response.

Previous studies in Uncaria tomentosa have shown promising results concerning the characterization of polyphenols with leaves yielding more diverse proanthocyanidins and higher bioactivities values. However, the polyphenols-microbiota interaction at the colonic level and their catabolites avoid the beneficial effects that can be exerted by this medicinal plant when consumed. In this regard, a new generation of hybrid nanoparticles has demonstrated improvements in natural compounds' activity by increasing their bioavailability. In this line, we report a detailed study of the characterization of a proanthocyanidin-enriched extract (PA-E) from U. tomentosa leaves from Costa Rica using UPLC-QTOF-ESI MS. Moreover, two types of hybrid nanoparticles, a polymeric-lipid (F-1) and a protein-lipid (F-2) loaded with PA-E were synthesized and their characterization was conducted by dynamic light scattering (DLS), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FT-IR), high-resolution transmission electron microscopy (HR-TEM), and encapsulation efficiency (%EE). In addition, in vitro release, antioxidant activity through 2,2-diphenyl-1-picrylhidrazyl (DPPH) as well as in vivo delayed-type hypersensitivity (DTH) reaction was evaluated. Results allowed the identification of 50 different compounds. The PA-E loaded nanoparticles F-1 and F-2 achieved encapsulation efficiency of ≥92%. The formulations exhibited porosity and spherical shapes with a size average of 26.1 ± 0.8 and 11.8 ± 3.3 nm for F-1 and F-2, respectively. PA-E increased its release rate from the nanoparticles compared to the free extract in water and antioxidant activity in an aqueous solution. In vivo, the delayed-type hypersensitive test shows the higher immune stimulation of the flavan-3-ols with higher molecular weight from U. tomentosa when administered as a nanoformulation, resulting in augmented antigen-specific responses. The present work constitutes to our knowledge, the first report on these bioactivities for proanthocyanidins from Uncaria tomentosa leaves when administrated by nanosystems, hence, enhancing the cellular response in mice, confirming their role in immune modulation.

Application of Poly-L-Lysine for Tailoring Graphene Oxide Mediated Contact Formation between Lithium Titanium Oxide LTO Surfaces for Batteries.

When producing stable electrodes, polymeric binders are highly functional materials that are effective in dispersing lithium-based oxides such as Li4Ti5O12 (LTO) and carbon-based materials and establishing the conductivity of the multiphase composites. Nowadays, binders such as polyvinylidene fluoride (PVDF) are used, requiring dedicated recycling strategies due to their low biodegradability and use of toxic solvents to dissolve it. Better structuring of the carbon layers and a low amount of binder could reduce the number of inactive materials in the electrode. In this study, we use computational and experimental methods to explore the use of the poly amino acid poly-L-lysine (PLL) as a novel biodegradable binder that is placed directly between nanostructured LTO and reduced graphene oxide. Density functional theory (DFT) calculations allowed us to determine that the (111) surface is the most stable LTO surface exposed to lysine. We performed Kubo-Greenwood electrical conductivity (KGEC) calculations to determine the electrical conductivity values for the hybrid LTO-lysine-rGO system. We found that the presence of the lysine-based binder at the interface increased the conductivity of the interface by four-fold relative to LTO-rGO in a lysine monolayer configuration, while two-stack lysine molecules resulted in 0.3-fold (in the plane orientation) and 0.26-fold (out of plane orientation) increases. These outcomes suggest that monolayers of lysine would specifically favor the conductivity. Experimentally, the assembly of graphene oxide on poly-L-lysine-TiO2 with sputter-deposited titania as a smooth and hydrophilic model substrate was investigated using a layer-by-layer (LBL) approach to realize the required composite morphology. Characterization techniques such as X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), Kelvin probe force microscopy (KPFM), scanning electron microscopy (SEM) were used to characterize the formed layers. Our experimental results show that thin layers of rGO were assembled on the TiO2 using PLL. Furthermore, the PLL adsorbates decrease the work function difference between the rGO- and the non-rGO-coated surface and increased the specific discharge capacity of the LTO-rGO composite material. Further experimental studies are necessary to determine the influence of the PLL for aspects such as the solid electrolyte interface, dendrite formation, and crack formation.

Bovine Serum Albumin-Based Nanoparticles: Preparation, Characterization, and Antioxidant Activity Enhancement of Three Main Curcuminoids from Curcuma longa.

Bovine Serum Albumin (BSA) lipid hybrid nanoparticles are part of the new solutions to overcome low bioavailability of poor solubility drugs such as curcuminoids, which possess multiple biological advantages; however, they are counterbalanced by its short biological half-life. In this line, we prepared the three main curcuminoids: curcumin (CUR), desmethoxycurcumin (DMC), and bisdemethoxycurcumin (BDM)-loaded BSA nanoparticles. The three formulations were characterized by the average size, size distribution, crystallinity, weight loss, drug release, kinetic mechanism, and antioxidant activity. The developed method produced CUR-, DMC-, and BDM-loaded BSA nanoparticles with a size average of 15.83 ± 0.18, 17.29 ± 3.34, and 15.14 ± 0.14 nm for CUR, DMC, and BDM loaded BSA, respectively. FT-IR analysis confirmed the encapsulation, and TEM images showed their spherical shape. The three formulations achieved encapsulation efficiency upper to 96% and an exhibited significantly increased release from the nanoparticle compared to free compounds in water. The antioxidant activity was enhanced as well, in agreement with the improvement in water release, obtaining IC50 values of 9.28, 11.70, and 15.19 µg/mL for CUR, DMC, and BDM loaded BSA nanoparticles, respectively, while free curcuminoids exhibited considerably lower antioxidant values in aqueous solution. Hence, this study shows promises for such hybrid systems, which have been ignored so far, regarding proper encapsulation, protection, and delivery of curcuminoids for the development of functional foods and pharmaceuticals.

Crystal Forms of the Antihypertensive Drug Irbesartan: A Crystallographic, Spectroscopic, and Hirshfeld Surface Analysis Investigation.

The design of new pharmaceutical solids with improved physical and chemical properties can be reached through in-detail knowledge of the noncovalent intermolecular interactions between the molecules in the context of crystal packing. Although crystallization from solutions is well-known for obtaining new solids, the effect of some variables on crystallization is not yet thoroughly understood. Among these variables, solvents are noteworthy. In this context, the present study aimed to investigate the effect of ethanol (EtOH), acetonitrile (MeCN), and acetone (ACTN) on obtaining irbesartan (IBS) crystal forms with 2,3-dibromosuccinic acid. Crystal structures were solved by single-crystal diffraction, and the intermolecular interactions were analyzed using the Hirshfeld surfaces analysis. The characterization of physicochemical properties was carried out by powder X-ray diffraction, Fourier transform infrared spectroscopy (FT-IR), thermal analysis, and solution-state NMR techniques. Two different IBS salts were obtained, one from MeCN and ACTN (compound 1) and a different one from EtOH (compound 2). The experimental results were in agreement with the findings obtained through quantum mechanics continuum solvation models. Compound 1 crystallized as a monoclinic system P21/c, whereas compound 2 in a triclinic system P1̅. In both structures, a net of strong hydrogen bonds is present, and their existence was confirmed by the FT-IR results. In addition, the IBS cation acts as a H-bond donor through the N1 and N6 nitrogen atoms which interact with the bromide anion and the water molecule O1W in compound 1. Meanwhile, N1 and N6 nitrogen atoms interact with the oxygen atoms provided by two symmetry-related 2,3-dibromo succinate anions in compound 2. Solution-state NMR data agreed with the protonation of the imidazolone ring in the crystal structure of compound 1. Both salts presented a different thermal behavior not only in melting temperature but also in thermal stability.

Evaluation of Piperine as Natural Coformer for Eutectics Preparation of Drugs Used in the Treatment of Cardiovascular Diseases.

Piperine (PIP) was evaluated as a natural coformer in the preparation of multicomponent organic materials for enhancing solubility and dissolution rate of the poorly water-soluble drugs: curcumin (CUR), lovastatin (LOV), and irbesartan (IBS). A screening based on liquid assisted grinding technique was performed using 1:1 drug-PIP molar ratio mixtures, followed by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) analyses. Three eutectic mixtures (EMs) composed of CUR-PIP, LOV-PIP, and IBS-PIP were obtained. Therefore, binary phase and Tamman's diagrams were constructed for each system to obtain the exact eutectic composition, which was 0.41:0.59, 0.29:0.71, and 0.31:0.69 for CUR-PIP, LOV-PIP, and IBS-PIP, respectively. Further, bulk materials of each system were prepared to characterize them through DSC, PXRD fully, Fourier transform infrared spectroscopy (FT-IR), and solution-state nuclear magnetic resonance (NMR) spectroscopy. In addition, the contact angle, solubility, and dissolution rate of each system were evaluated. The preserved characteristic in the PXRD patterns and FT-IR spectra of the bulk material of each system confirmed the formation of EM mixture without molecular interaction in solid-state. The formation of EM resulted in improved aqueous solubility and dissolution rate associated with the increased wettability observed by the decrease in contact angle. In addition, solution NMR analyses of CUR-PIP, LOV-PIP, and IBS-PIP suggested no significant intermolecular interactions in solution between the components of the EM. Hence, this study concludes that PIP could be an effective coformer to improve the solubility and dissolution rate of CUR, LOV, and IBS.

Interaction and Compatibility Studies in the Development of Olmesartan Medoxomil and Hydrochlorothiazide Formulations under a Real Manufacturing Process.

A drug-drug and drug-excipient interactions and compatibilities study was conducted for two fixed-dose combination (FDC) products containing olmesartan medoxomil (OLM)/hydrochlorothiazide (HCT) 20/12.5 mg and OLM/HCT 40/12.5 mg during their development including storage. The study consisted of the evaluation of samples retrieved during all stages of a real manufacturing process. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transform infrared spectroscopy (FT-IR), and contact angle techniques were applied to the samples to determine interactions and incompatibilities. Dissolution tests and long-term stability studies were conducted to evaluate dosage form performance. Results showed weak solid-state interactions able to obtain a eutectic mixture of OLM and HCT while microcrystalline cellulose (MC) impacted the thermal stability of both drugs. Reliable dissolution and long-term stability tests confirmed that the interactions observed were not considered incompatibilities because they were not influenced by the performance of the final products.

Novel pathway for the sonochemical synthesis of silver nanoparticles with near-spherical shape and high stability in aqueous media.

The present study shows the development of a novel sonochemical synthesis pathway of sub-15 nm silver nanoparticles (AgNPs) with quasi-spherical shape and high stability in aqueous suspension. Different analytical techniques such as on-line UV-Vis spectroscopy, Atomic Force Microscopy (AFM), and Transmission Electron Microscopy (TEM) were complementarily used to characterize the evolution of the properties of AgNPs synthesized with this new route. Furthermore, different centrifugation conditions were studied to establish a practical, simple and straightforward purification method. Particle size was determined by TEM employing two different deposition methods, showing that purified AgNPs have a size of 8.1 nm ± 2.4 nm with a narrow dispersion of the size distribution (95% coverage interval from 3.4 to 13 nm). Critical information of the shape and crystalline structure of these sub-15 nm AgNPs, provided by shape descriptors (circularity and roundness) using TEM and high resolution (HR)-TEM measurements, confirmed the generation of AgNPs with quasi-spherical shapes with certain twin-fault particles promoted by the high energy of the ultrasonic treatment. Elemental analysis by TEM-EDS confirmed the high purity of the sub-15 nm AgNPs, consisting solely of Ag. At the optical level, these AgNPs showed a bandgap energy of (2.795 ± 0.002) eV. Finally, the evaluation of the effects of ultraviolet radiation (UVC: 254 nm and UVA: 365 nm) and storage temperature on the spectral stability revealed high stability of the optical properties and subsequently dimensional properties of sub-15 nm AgNPs in the short-term (600 min) and long-term (24 weeks).

Effects of heat on seven endodontic sealers.

PURPOSE: To examine the microscopic surface features, chemical composition, and thermodynamic profile of seven endodontic sealers (AH Plus, Adseal, MTA-Fillapex, RoekoSeal, GuttaFlow 2, GuttaFlow BioSeal, and EndoRez) exposed to high-temperature changes using an endodontic obturation device. METHODS: The thermal properties were examined using scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Then, six disc-shaped specimens of each sealer were prepared and divided into two groups - a room temperature group and a heat exposure group - for analysis of surface and chemical changes using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). RESULTS: DSC analysis showed that AH Plus had the highest exothermal signal (122.9°C), while TGA analysis showed that MTA-Fillapex was most affected by increased temperature (32.4% mass loss at 230ºC). SEM analysis showed that while AH Plus and GuttaFlow BioSeal maintained their surface integrity after heat exposure, the EDS profiles demonstrated changes in the chemical composition of the sealers after heat exposure for 5 s. High-temperature exposure had a negative impact on the properties of five of the sealers (Adseal, MTA-Fillapex, RoekoSeal, GuttaFlow 2, and EndoRez). CONCLUSION: AH Plus and GuttaFlow BioSeal showed minimal changes upon high-temperature exposure, suggesting their suitability for thermal endodontic obturation techniques.

Design of Hybrid Polymeric-Lipid Nanoparticles Using Curcumin as a Model: Preparation, Characterization, and In Vitro Evaluation of Demethoxycurcumin and Bisdemethoxycurcumin-Loaded Nanoparticles.

Polymeric lipid hybrid nanoparticles (PLHNs) are the new generation of drug delivery systems that has emerged as a combination of a polymeric core and lipid shell. We designed and optimized a simple method for the preparation of Pluronic F-127-based PLHNs able to load separately demethoxycurcumin (DMC) and bisdemethoycurcumin (BDM). CUR was used as a model compound due to its greater availability from turmeric and its structure similarity with DMC and BDM. The developed method produced DMC and BDM-loaded PLHNs with a size average of 75.55 ± 0.51 and 15.13 ± 0.014 nm for DMC and BDM, respectively. An FT-IR analysis confirmed the encapsulation and TEM images showed their spherical shape. Both formulations achieved an encapsulation efficiency ≥ 92% and an exhibited significantly increased release from the PLHN compared with free compounds in water. The antioxidant activity was enhanced as well, in agreement with the improvement in water dissolution; obtaining IC50 values of 12.74 ± 0.09 and 16.03 ± 0.55 for DMC and BDM-loaded PLHNs, respectively, while free curcuminoids exhibited considerably lower antioxidant values in an aqueous solution. Hence, the optimized PHLN synthesis method using CUR as a model and then successfully applied to obtain DMC and BDM-loaded PLHNs can be extended to curcuminoids and molecules with a similar backbone structure to improve their bioactivities.