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1.
PLoS One ; 19(5): e0302142, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38722957

RESUMEN

We explore theoretically Goos-Hänchen (GH) shift around the defect mode in superconducting defective photonic crystals (PCs) in cryogenic environment. The defective PCs are constructed by alternating semiconductors and superconductors. A defect mode arises in the photonic bandgap and sensitively depends on environment temperature and hydrostatic pressure. Reflection and transmission coefficient phases make an abruptly jump at the defect mode and giant GH shifts have been achieved around this mode. The maximum GH shift can get as high as 103λ (incident wavelength), which could be modulated by the values of temperature and hydrostatic pressure. This study may be utilized for pressure- or temperature-sensors in cryogenic environment.


Asunto(s)
Fotones , Cristalización , Superconductividad , Semiconductores , Presión Hidrostática , Temperatura
2.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38731865

RESUMEN

This study explored the feasibility of fluoride removal from simulated semiconductor industry wastewater and its recovery as calcium fluoride using fluidized bed crystallization. The continuous reactor showed the best performance (>90% fluoride removal and >95% crystallization efficiency) at a calcium-to-fluoride ratio of 0.6 within the first 40 days of continuous operation. The resulting particle size increased by more than double during this time, along with a 36% increase in the seed bed height, indicating the deposition of CaF2 onto the silica seed. The SEM-EDX analysis showed the size and shape of the crystals formed, along with the presence of a high amount of Ca-F ions. The purity of the CaF2 crystals was determined to be 91.1% though ICP-OES analysis. Following the continuous experiment, different process improvement strategies were explored. The addition of an excess amount of calcium resulted in the removal of an additional 6% of the fluoride; however, compared to this single-stage process, a two-stage approach was found to be a better strategy to achieve a low effluent concentration of fluoride. The fluoride removal reached 94% with this two-stage approach under the optimum conditions of 4 + 1 h HRT combinations and a [Ca2+]/[F-] ratio of 0.55 and 0.7 for the two reactors, respectively. CFD simulation showed the impact of the inlet diameter, bottom-angle shape, and width-to-height ratio of the reactor on the mixing inside the reactor and the possibility of further improvement in the reactor performance by optimizing the FBR configuration.


Asunto(s)
Fluoruro de Calcio , Fluoruros , Aguas Residuales , Fluoruro de Calcio/química , Fluoruros/química , Fluoruros/aislamiento & purificación , Aguas Residuales/química , Purificación del Agua/métodos , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/aislamiento & purificación , Cristalización
3.
Cryo Letters ; 45(3): 185-193, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38709190

RESUMEN

BACKGROUND: Characterization of intracellular ice formation (IIF) in oocytes during the freezing and thawing processes will contribute to optimizing their cryopreservation. However, the observation of the ice formation process in oocytes is limited by the spatiotemporal resolution of the cryomicroscope systems. OBJECTIVE: To observe the intracellular icing of oocytes during cooling and rewarming, and to study the mechanism of formation and growth of intracellular ice in oocytes. MATERIALS AND METHODS: Mouse oocytes were frozen at different cooling rates to induce intracellular ice formation using a cryomicroscopy system consisting of a microscope equipped with a cryogenic cold stage, an automatic cooling system, a temperature control system, and a high-speed camera. The growth patterns of intracellular ice in oocytes were analyzed from the images recorded. Finally, the growth rate of intracellular ice formation in oocytes was calculated using an automatic intracellular ice tracking method. RESULTS: The IIF temperature decreased gradually with the increase in cooling rate. Initiation sites of IIF could be classified into three categories: marginal type, internal type and coexisting type. There was a strong predominance for ice crystal initiation site in the oocytes, with up to 80% of the initiation sites located in the marginal region. The intracellular ice growth modes of darkening and twitching cells were characterized by "spreading" and "clustering", respectively. In addition, twitching cells started to recrystallize during rewarming, while darkening cells did not. The instantaneous maximal growth rate of ice crystals in twitching cells was about 10 times higher than that in darkening cells. CONCLUSION: By visualising the growth of ice crystals in mouse oocytes during cooling and rewarming, we obtained valuable information on the kinetics of ice formation and melting in these cells. This information can help us understand how ice formation and melting affect the viability and quality of oocytes after cryopreservation. Doi.org/10.54680/fr24310110412.


Asunto(s)
Criopreservación , Hielo , Oocitos , Animales , Ratones , Oocitos/citología , Oocitos/fisiología , Criopreservación/métodos , Femenino , Congelación , Cristalización , Microscopía/métodos
4.
AAPS PharmSciTech ; 25(5): 103, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714634

RESUMEN

Crystallization of amorphous pharmaceutical solids are widely reported to be affected by the addition of polymer, while the underlying mechanism require deep study. Herein, crystal growth behaviors of glassy griseofulvin (GSF) doped with various 1% w/w polymer were systematically studied. From the molecular structure, GSF cannot form the hydrogen bonding interactions with the selected polymer poly(vinyl acetate), polyvinyl pyrrolidone (PVP), 60:40 vinyl pyrrolidone-vinyl acetate copolymer (PVP/VA 64), and poly(ethylene oxide) (PEO). 1% w/w polymer exhibited weak or no detectable effects on the glass transition temperature (Tg) of GSF. However, crystal growth rates of GSF was altered from 4.27-fold increase to 2.57-fold decrease at 8 ℃ below Tg of GSF. Interestingly, the ability to accelerate and inhibit the growth rates of GSF crystals correlated well with Tg of polymer, indicating the controlling role of segmental mobility of polymer. Moreover, ring-banded growth of GSF was observed in the polymer-doped systems. Normal compact bulk and ring-banded crystals of GSF were both characterized as the thermodynamically stable form I. More importantly, formation of ring-banded crystals of GSF can significantly weaken the inhibitory effects of polymer on the crystallization of glassy GSF.


Asunto(s)
Cristalización , Griseofulvina , Polímeros , Temperatura de Transición , Griseofulvina/química , Cristalización/métodos , Polímeros/química , Estabilidad de Medicamentos , Enlace de Hidrógeno , Polivinilos/química , Polietilenglicoles/química , Povidona/química , Vidrio/química
6.
Colloids Surf B Biointerfaces ; 238: 113913, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38608463

RESUMEN

A gout attack could be viewed as a nucleation event. Many reports have shown that the typical molecular structure of crystallization inhibitors usually contains carboxyl and hydroxyl groups, which could interact with solute molecules through hydrogen bonding, thereby suppressing the nucleation and growth of crystals. Since 1923, l-lactic acid (LA), a molecule with structural features of inhibitors, has been speculated to be a trigger for acute gout because metabolized LA temporarily reduces uric acid excretion and leads to a slow increase in serum uric acid concentration. However, many cases of gout presumably triggered by elevated lactate in a very short period of 4 h are often inexplicable. Here, we present the unexpected result that LA has a significant "opposite effect" on the nucleation and growth of gouty pathological crystals, which is that as the concentration of the additive LA increases, the nucleation and growth of the crystals is suppressed and then facilitated. This approach may help our clarifying the long-standing "misunderstandings" and further understanding the association between metabolized LA and increased risk of gout attacks. Finally, a novel mechanism called "tailed-made occupancy (TMO)" was used to explain the nucleation and crystallization effects of LA on sodium urate monohydrate (MSUM).


Asunto(s)
Cristalización , Gota , Ácido Láctico , Ácido Úrico , Gota/metabolismo , Ácido Láctico/química , Ácido Láctico/metabolismo , Humanos , Ácido Úrico/química , Ácido Úrico/metabolismo
7.
Chemosphere ; 357: 142008, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38614398

RESUMEN

The mixture of copper and iron often results in materials with favorable properties. The material production processes involving these metals including electroplating produce hazardous wastewater. In this study, the Fluidized Bed Homogeneous Crystallization (FBHC) process was applied to treat iron and copper-containing wastewater. The initial iron copper particles were successfully recovered from synthetic wastewater with [Fe]0:[Cu]0 of 2:1, the total metal concentration of 3 mM, at effluent pH = 7.75 ± 0.75, with the upflow velocity (U) of 1.76 m/h. The agglomerates hardening process is a crucial step for initial particle synthesis. The SEM analysis reveals the spherical particle's densified crust and porous core. The particle formation mechanism which includes the formation of the nucleus, attachment of precipitate flakes, and densification of particles was proposed after microscopic observation. The initial particles synthesized were used to initiate the treatment of synthetic wastewater at the operating condition pH = 7.75 ± 0.5, [Fe]0:[Cu]0 of 2:1, the total metal concentration of 3 mM, [CO32-]0:[M]0 = 1.2:1, and U of 28.66 m/h which results in the total metal removal of 99% and crystallization ratio of 90% and 88% for iron and copper respectively. The conditions were then applied to treat electroplating wastewater and resulted in the total metal removal of 99% for both iron and copper and a crystallization ratio of 83% and 79% for iron and copper, respectively. The treatment provided advantages in terms of treating larger amounts of sludge while eliminating the need to provide seed thus yielding a higher purity of product.


Asunto(s)
Cobre , Cristalización , Hierro , Eliminación de Residuos Líquidos , Aguas Residuales , Contaminantes Químicos del Agua , Aguas Residuales/química , Cobre/química , Cobre/aislamiento & purificación , Hierro/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Eliminación de Residuos Líquidos/métodos
8.
Int J Biol Macromol ; 267(Pt 1): 131268, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38580011

RESUMEN

Human carbonic anhydrases (hCAs) play a central role in various physiological processes in the human body. HCAs catalyze the reversible hydration of CO2 into HCO3-, and hence maintains the fluid and pH balance. Overexpression of CA II is associated with diseases, such as glaucoma, and epilepsy. Therefore, CAs are important clinical targets and inhibition of different isoforms, especially hCA II is used in treatment of glaucoma, altitude sickness, and epilepsy. Therapeutically used CA inhibitors (CAI) are sulfonamide-based, such as acetazolamide, dichlorphenamide, methazolamide, ethoxzolamide, etc. However, they exhibit several undesirable effects such as numbness, tingling of extremities, malaise, metallic taste, fatigue, renal calculi, and metabolic acidosis. Therefore, there is an urgent need to identify safe and effective inhibitors of the hCAs. In this study, different phenyl boronic acids 1-5 were evaluated against bovine (bCA II) and hCA II. Among all, compound 1 (4-acetylphenyl boronic acid) was found to be active against bCAII and hCA II with IC50 values of 246 ± 0.48 and 281.40 ± 2.8 µM, respectively, while the remaining compounds were found in-active. Compound 1 was identified as competitive inhibitor of hCA II enzyme (Ki = 283.7 ± 0.002 µM). Additionally, compound 1 was found to be non-toxic against BJ Human fibroblast cell line. The X-ray crystal structure for hCA II in-complex with compound 1 was evaluated to a resolution of 2.6 Å. In fact, this the first structural analysis of a phenyl boron-based inhibitor bound to hCA II, allowing an additional structure-activity analysis of the compounds. Compound 1 was found to be directly bound in the active site of hCA II by interacting with His94, His119, and Thr199 residues. In addition, a bond of 3.11 Å between the zinc ion and coordinated boron atom of the boronic acid moiety of compound 1 was also observed, contributing to binding affinity of compound 1 for hCA II. PDB ID: 8IGF.


Asunto(s)
Ácidos Borónicos , Anhidrasa Carbónica II , Inhibidores de Anhidrasa Carbónica , Inhibidores de Anhidrasa Carbónica/química , Inhibidores de Anhidrasa Carbónica/farmacología , Humanos , Ácidos Borónicos/química , Ácidos Borónicos/farmacología , Anhidrasa Carbónica II/antagonistas & inhibidores , Anhidrasa Carbónica II/química , Anhidrasa Carbónica II/metabolismo , Cristalografía por Rayos X , Cristalización , Animales , Bovinos , Modelos Moleculares , Relación Estructura-Actividad
9.
Methods Mol Biol ; 2787: 333-353, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38656501

RESUMEN

X-ray crystallography is a robust and widely used technique that facilitates the three-dimensional structure determination of proteins at an atomic scale. This methodology entails the growth of protein crystals under controlled conditions followed by their exposure to X-ray beams and the subsequent analysis of the resulting diffraction patterns via computational tools to determine the three-dimensional architecture of the protein. However, achieving high-resolution structures through X-ray crystallography can be quite challenging due to complexities associated with protein purity, crystallization efficiency, and crystal quality.In this chapter, we provide a detailed overview of the gene to structure determination pipeline used in X-ray crystallography, a crucial tool for understanding protein structures. The chapter covers the steps in protein crystallization, along with the processes of data collection, processing, structure determination, and refinement. The most commonly faced challenges throughout this procedure are also addressed. Finally, the importance of standardized protocols for reproducibility and accuracy is emphasized, as they are crucial for advancing the understanding of protein structure and function.


Asunto(s)
Cristalización , Conformación Proteica , Proteínas , Cristalografía por Rayos X/métodos , Proteínas/química , Cristalización/métodos , Modelos Moleculares , Programas Informáticos
10.
Int J Mol Sci ; 25(8)2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38673982

RESUMEN

The research presented in this article focuses on the use of inorganic-organic material, based on titanium dioxide and lignin, as a filler for polylactide (PLA) biocomposites. To date, no research has been conducted to understand the impact of hybrid fillers consisting of TiO2 and lignin on the supermolecular structure and crystallization abilities of polylactide. Polymer composites containing 1, 3 or 5 wt.% of hybrid filler or TiO2 were assessed in terms of their structure, morphology, and thermal properties. Mechanical properties, including tensile testing, bending, impact strength, and hardness, were discussed. The hybrid filler is characterized by a very good electrokinetic stability at pH greater than 3-4. The addition of all fillers led to a small decrease in the glass transition temperature but, most importantly, the addition of 1% of the hybrid filler to the PLA matrix increased the degree of crystallinity of the material by up to 20%. Microscopic studies revealed differences in the crystallization behavior and nucleation ability of fillers. The use of hybrid filler resulted in higher nucleation density and shorter induction time than in unfilled PLA or PLA with only TiO2. The introduction of small amounts of hybrid filler also affected the mechanical properties of the composites, causing an increase in bending strength and hardness. This information may be useful from a technological process standpoint and may also help to increase the range of applicability of biobased materials.


Asunto(s)
Lignina , Poliésteres , Titanio , Titanio/química , Poliésteres/química , Lignina/química , Cristalización , Resistencia a la Tracción , Ensayo de Materiales , Dureza
11.
J Mater Chem B ; 12(18): 4509-4520, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38647022

RESUMEN

One of the key challenges in diagnosing thyroid cancer lies in the substantial percentage of indeterminate diagnoses of thyroid nodules that have undergone ultrasound-guided fine-needle aspiration (FNA) biopsy for cytological evaluation. This delays the definitive diagnosis and treatment plans. We recently demonstrated that hydroxyapatite microcalcifications (MCs) aspirated from thyroid nodules may aid nodule diagnosis based on their composition. In particular, Zn-enriched MCs have emerged as potential cancer biomarkers. However, a pertinent question remains: is the elevated Zn content within MCs a consequence of cancer, or do the Zn-enriched MCs encourage tumorigenesis? To address this, we treated the human thyroid cancer cell line MDA-T32 with synthetic MC analogs comprising hydroxyapatite crystals with varied pathologically relevant Zn fractions and assessed the cellular response. The MC analogs exhibited an irregular surface morphology similar to FNA MCs observed in cancerous thyroid nodules. These MC analogs displayed an inverse relationship between Zn fraction and crystallinity, as shown by X-ray diffractometry. The zeta potential of the non-Zn-bearing hydroxyapatite crystals was negative, which decreased once Zn was incorporated into the crystal. The MC analogs were not cytotoxic. The cellular response to exposure to these crystals was evaluated in terms of cell migration, proliferation, the tendency of the cells to form multicellular spheroids, and the expression of cancer markers. Our findings suggest that, if thyroid MCs play a role in promoting cancerous behavior in vivo, it is likely a result of the interplay of crystallinity with Zn and carbonate fractions in MCs.


Asunto(s)
Calcinosis , Neoplasias de la Tiroides , Zinc , Humanos , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/metabolismo , Zinc/química , Calcinosis/patología , Calcinosis/metabolismo , Carbonatos/química , Cristalización , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Durapatita/química
12.
Metallomics ; 16(5)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38599629

RESUMEN

Taking into account that in recent decades there has been an increase in the incidence of urinary stones, especially in highly developed countries, from a wide range of potentially harmful substances commonly available in such countries, we chose zinc for the research presented in this article, which is classified by some sources as a heavy metal. In this article, we present the results of research on the influence of Zn2+ ion on the nucleation and growth of struvite crystals-the main component of infection urinary stones. The tests were carried out in an artificial urine environment with and without the presence of Proteus mirabilis bacteria. In the latter case, the activity of bacterial urease was simulated chemically, by systematic addition of an aqueous ammonia solution. The obtained results indicate that Zn2+ ions compete with Mg2+ ions, which leads to the gradual replacement of Mg2+ ions in the struvite crystal lattice with Zn2+ ions to some extent. This means co-precipitation of Mg-struvite (MgNH4PO4·6H2O) and Znx-struvite (Mg1-xZnxNH4PO4·6H2O). Speciation analysis of chemical complexes showed that Znx-struvite precipitates at slightly lower pH values than Mg-struvite. This means that Zn2+ ions shift the nucleation point of crystalline solids towards a lower pH. Additionally, the conducted research shows that Zn2+ ions, in the range of tested concentrations, do not have a toxic effect on bacteria; on the contrary, it has a positive effect on cellular metabolism, enabling bacteria to develop better. It means that Zn2+ ions in artificial urine, in vitro, slightly increase the risk of developing infection urinary stones.


Asunto(s)
Proteus mirabilis , Estruvita , Cálculos Urinarios , Zinc , Estruvita/química , Zinc/metabolismo , Zinc/química , Cálculos Urinarios/química , Cálculos Urinarios/metabolismo , Cálculos Urinarios/microbiología , Proteus mirabilis/metabolismo , Humanos , Fosfatos/metabolismo , Fosfatos/química , Iones , Compuestos de Magnesio/metabolismo , Compuestos de Magnesio/química , Cristalización
13.
Discov Med ; 36(183): 799-815, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38665028

RESUMEN

BACKGROUND: Calcium oxalate monohydrate (COM) forms the most common type of kidney stones observed in clinics, elevated levels of urinary oxalate being the principal risk factor for such an etiology. The objective of the present study was to evaluate the anti-nephrolithiatic effect of herbo-mineral formulation, Lithom. METHODS: The in vitro biochemical synthesis of COM crystals in the presence of Lithom was performed and observations were made by microscopy and Scanning Electron Microscope (SEM) based analysis for the detection of crystal size and morphology. The phytochemical composition of Lithom was evaluated by Ultra-High-Performance Liquid Chromatography (UHPLC). The in vivo model of Ethylene glycol-induced hyperoxaluria in Sprague-Dawley rats was used for the evaluation of Lithom. The animals were randomly allocated to 5 different groups namely Normal control, Disease control (ethylene glycol (EG), 0.75%, 28 days), Allopurinol (50 mg/kg, q.d.), Lithom (43 mg/kg, b.i.d.), and Lithom (129 mg/kg, b.i.d.). Analysis of crystalluria, oxalate, and citrate levels, oxidative stress parameters (malondialdehyde (MDA), catalase, myeloperoxidase (MPO)), and histopathology by hematoxylin and eosin (H&E) and Von Kossa staining was performed for evaluation of Lithom. RESULTS: The presence of Lithom during COM crystals synthesis significantly reduced the average crystal area, feret's diameter, and area-perimeter ratio, in a dose-dependent manner. SEM analysis revealed that COM crystals synthesized in the presence of 100 and 300 µg/mL of Lithom exhibited a veritable morphological transition from irregular polygons with sharp edges to smoothened smaller cuboid polygons. UHPLC analysis of Lithom revealed the presence of Trigonelline, Bergenin, Xanthosine, Adenosine, Bohoervinone B, Vanillic acid, and Ellagic acid as key phytoconstituents. In EG-induced SD rats, the Lithom-treated group showed a decrease in elevated urinary oxalate levels, oxidative stress, and renal inflammation. Von Kossa staining of kidney tissue also exhibited a marked reduction in crystal depositions in Lithom-treated groups. CONCLUSION: Taken together, Lithom could be a potential clinical-therapeutic alternative for management of nephrolithiasis.


Asunto(s)
Oxalato de Calcio , Modelos Animales de Enfermedad , Hiperoxaluria , Nefrolitiasis , Estrés Oxidativo , Ratas Sprague-Dawley , Animales , Oxalato de Calcio/metabolismo , Oxalato de Calcio/química , Hiperoxaluria/inducido químicamente , Hiperoxaluria/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Nefrolitiasis/inducido químicamente , Nefrolitiasis/metabolismo , Nefrolitiasis/patología , Masculino , Cristalización , Glicol de Etileno/toxicidad , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico
14.
J Biomed Mater Res B Appl Biomater ; 112(5): e35408, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38676958

RESUMEN

Gelatin methacrylate (GelMA) hydrogels are expected to be ideal skin tissue engineering dressings for a wide range of clinical treatments. Herein, we report the preparation of GelMA or antifreeze GelMA hydrogel sheets with different GelMA concentrations, crosslinking times, and cryoprotectant (CPA) concentrations. The crystallization properties of GelMA or antifreeze GelMA hydrogel sheets were studied by cryomicroscopy and differential scanning calorimetry (DSC). It was found that the growth of ice crystals was slower when GelMA hydrogel concentration was more than 7%. The 10% DMSO-7% GelMA hydrogel sheets crosslinked for 60 min showed no ice crystal formation and growth during cooling and warming. The DSC results showed that the vitrification temperature of the 10% DMSO-7% GelMA hydrogel sheet was -111°C. Furthermore, slow freezing and rapid freezing of fibroblast-laden GelMA or antifreeze GelMA hydrogel sheets, and tissue-engineered skin constructs were studied. The results showed no significant difference in cell survival between slow (88.8% ± 1.51) and rapid (89.2% ± 3.00) freezing of fibroblast-loaded 10% DMSO-7% GelMA hydrogel sheets, and significantly higher than that of 7% GelMA hydrogel sheets (33.4% ± 5.46). The cell viability was higher in tissue-engineered skin constructs after slow freezing (86.34% ± 1.45) than rapid freezing (72.74% ± 1.34). We believe that the combination of antifreeze hydrogels and tissue engineering will facilitate the cryopreservation of tissue engineering constructs.


Asunto(s)
Criopreservación , Fibroblastos , Gelatina , Hidrogeles , Ingeniería de Tejidos , Hidrogeles/química , Hidrogeles/farmacología , Gelatina/química , Animales , Fibroblastos/citología , Fibroblastos/metabolismo , Cristalización , Crioprotectores/farmacología , Crioprotectores/química , Metacrilatos/química , Piel/metabolismo , Ratones , Proteínas Anticongelantes/química , Proteínas Anticongelantes/farmacología , Humanos , Supervivencia Celular/efectos de los fármacos
15.
Int J Pharm ; 656: 124108, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38604540

RESUMEN

Lipid-based formulations (LbFs) are an extensively used approach for oral delivery of poorly soluble drug compounds in the form of lipid suspension and lipid solution. However, the high target dose and inadequate lipid solubility limit the potential of brick dust molecules to be formulated as LbFs. Thus, the complexation of such molecules with a lipophilic counterion can be a plausible approach to improve the solubility in lipid-based solutions via reducing drug crystallinity and polar surface area. The study aimed to enhance drug loading in lipid solution for Nilotinib (Nil) through complexation or salt formation with different lipophilic counterions. We synthesized different lipophilic salts/ complexes via metathesis reactions and confirmed their formation by 1H NMR and FTIR. Docusate-based lipophilic salt showed improved solubility in medium-chain triglycerides (∼7 to 7.5-fold) and long-chain triglycerides (∼30 to 35-fold) based lipids compared to unformulated crystalline Nil. The increased lipid solubility could be attributed to the reduction in drug crystallinity which was further confirmed by the PXRD and DSC. Prototype LbFs were prepared to evaluate drug loading and their physicochemical characteristics. The findings suggested that structural features of counterion including chain length and lipophilicity affect the drug loading in LbF. In addition, physical stability testing of formulations was performed, inferring that aliphatic sulfate-based LbFs were stable with no sign of drug precipitation or salt disproportionation. An in vitro lipolysis-permeation study revealed that the primary driver of absorptive flux is the solubilization of the drug and reduced amount of lipid. Further, the in vivo characterization was conducted to measure the influence of increased drug load on oral bioavailability. Overall, the results revealed enhanced absorption of lipophilic salt-based LbF over unformulated crystalline Nil and conventional LbF (drug load equivalent to equilibrium solubility) which supports the idea that lipophilic salt-based LbF enhances drug loading, and supersaturation-mediated drug solubilization, unlocking the full potential of LbF.


Asunto(s)
Lípidos , Sales (Química) , Solubilidad , Sales (Química)/química , Animales , Lípidos/química , Masculino , Administración Oral , Composición de Medicamentos/métodos , Pirimidinas/química , Pirimidinas/administración & dosificación , Pirimidinas/farmacocinética , Polvo , Liberación de Fármacos , Ratas , Química Farmacéutica/métodos , Interacciones Hidrofóbicas e Hidrofílicas , Triglicéridos/química , Estabilidad de Medicamentos , Portadores de Fármacos/química , Cristalización
16.
AAPS PharmSciTech ; 25(4): 84, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38605282

RESUMEN

The present work aims to explore the new solid forms of telmisartan (TEL) with alpha-ketoglutaric acid (KGA) and glutamic acid (GA) as potential coformers using mechanochemical approach and their role in augmentation in physicochemical parameters over pure crystalline TEL. Mechanochemical synthesis was performed using 1:1 stoichiometric ratio of TEL and the selected coformers in the presence of catalytic amount of ethanol for 1 h. The ground product was characterized by PXRD, DSC, and FTIR. The new solid forms were evaluated for apparent solubility, intrinsic dissolution, and physical stability. Preliminary characterization revealed the amorphization of the mechanochemical product as an alternate outcome of cocrystallization screening. Mechanistic understanding of the amorphous phase highlights the formation of amorphous-mediated cocrystallization that involves three steps, viz., molecular recognition, intermediate amorphous phase, and product nucleation. The solubility curves of both multicomponent amorphous solid forms (TEL-KGA and TEL-GA) showed the spring-parachute effect and revealed significant augmentation in apparent solubility (8-10-folds), and intrinsic dissolution release (6-9-folds) as compared to the pure drug. Besides, surface anisotropy and differential elemental distributions in intrinsic dissolution compacts of both solid forms were confirmed by FESEM and EDX mapping. Therefore, amorphous phases prepared from mechanochemical synthesis can serve as a potential solid form for the investigation of a cocrystal through amorphous-mediated cocrystallization. This has greater implications in solubility kinetics wherein the rapid precipitation of the amorphous phase can be prevented by the metastable cocrystal phase and contribute to the significant augmentation in the physicochemical parameters.


Asunto(s)
Telmisartán , Cristalización , Solubilidad , Estabilidad de Medicamentos
17.
Int J Mol Sci ; 25(7)2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38612770

RESUMEN

This study utilized a fluidized bed reactor (FBR) for fluoride removal from high-concentration fluoride-ion-containing simulated semiconductor industry wastewater and recovered high-purity CaF2 crystals. The effects of hydraulic retention time (HRT), pH, Ca2+ to F- ratio, upflow velocity, seed size and seed bed height were investigated by performing lab-scale batch experiments. Considering fluoride removal and CaF2 crystallization efficiency, 5 h HRT, pH 6, seed height of 50 cm and [Ca2+]/[F-] ratio of 0.55 (mol/mol) were found to be optimum. The effect of the interaction between the important process parameters on fluoride removal was further analyzed using response surface methodology (RSM) experimental design. The results showed that all the individual parameters have a significant impact (p = 0.0001) on fluoride removal. SEM-EDX and FTIR analysis showed the composition of the crystals formed inside FBR. HR-XRD analysis confirmed that the crystalline structure of samples was mainly CaF2. The results clearly demonstrated the feasibility of silica seed material containing FBR for efficient removal and recovery of fluoride as high-purity calcium fluoride crystals.


Asunto(s)
Fluoruro de Calcio , Fluoruros , Aguas Residuales , Cristalización , Semiconductores
18.
Molecules ; 29(8)2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38675529

RESUMEN

It is well known that daidzein has various significant medicinal values and health benefits, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, cholesterol lowering, neuroprotective, cardioprotective and so on. To our disappointment, poor solubility, low permeability and inferior bioavailability seriously limit its clinical application and market development. To optimize the solubility, permeability and bioavailability of daidzein, the cocrystal of daidzein and piperazine was prepared through a scientific and reasonable design, which was thoroughly characterized by single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Combining single-crystal X-ray diffraction analysis with theoretical calculation, detailed structural information on the cocrystal was clarified and validated. In addition, a series of evaluations on the pharmacogenetic properties of the cocrystal were investigated. The results indicated that the cocrystal of daidzein and piperazine possessed the favorable stability, increased solubility, improved permeability and optimized bioavailability of daidzein. Compared with the parent drug, the formation of cocrystal, respectively, resulted in 3.9-, 3.1-, 4.9- and 60.8-fold enhancement in the solubility in four different media, 4.8-fold elevation in the permeability and 3.2-fold in the bioavailability of daidzein. Targeting the pharmaceutical defects of daidzein, the surprising elevation in the solubility, permeability and bioavailability of daidzein was realized by a clever cocrystal strategy, which not only devoted assistance to the market development and clinical application of daidzein but also paved a new path to address the drug-forming defects of insoluble drugs.


Asunto(s)
Disponibilidad Biológica , Isoflavonas , Permeabilidad , Piperazina , Solubilidad , Isoflavonas/química , Isoflavonas/farmacocinética , Piperazina/química , Cristalización , Difracción de Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , Animales , Cristalografía por Rayos X , Rastreo Diferencial de Calorimetría , Humanos
19.
Molecules ; 29(8)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38675667

RESUMEN

The process of lipid crystallization influences the characteristics of lipid. By changing the chemical composition of the lipid system, the crystallization behavior could be controlled. This review elucidates the internal factors affecting lipid crystallization, including triacylglycerol (TAG) structure, TAG composition, and minor components. The influence of these factors on the TAG crystal polymorphic form, nanostructure, microstructure, and physical properties is discussed. The interplay of these factors collectively influences crystallization across various scales. Variations in fatty acid chain length, double bonds, and branching, along with their arrangement on the glycerol backbone, dictate molecular interactions within and between TAG molecules. High-melting-point TAG dominates crystallization, while liquid oil hinders the process but facilitates polymorphic transitions. Unique molecular interactions arise from specific TAG combinations, yielding molecular compounds with distinctive properties. Nanoscale crystallization is significantly impacted by liquid oil and minor components. The interaction between the TAG and minor components determines the influence of minor components on the crystallization process. In addition, future perspectives on better design and control of lipid crystallization are also presented.


Asunto(s)
Cristalización , Triglicéridos , Triglicéridos/química , Lípidos/química , Ácidos Grasos/química
20.
Anal Chem ; 96(17): 6700-6706, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38621112

RESUMEN

Photonic crystals with specific wavelengths can realize surface-enhanced excitation and emission intensities of fluorophores and enhance the fluorescence signals of fluorescent molecules. Herein, stretchable photonic crystals with good mechanochromic properties provide continuously adjustable forbidden wavelengths by stretching to change the lattice spacing, with reflectance peaks blue-shifted up to 110 nm to match indicators of different wavelengths and produce differentiated optical enhancement effects. Glycoproteins are significantly identified as clinical markers. However, the wide participation of glycoproteins in various life processes poses enormous complexity and critical challenges for rapid, facile, high-throughput, and accurate clinical analysis or health assessment. In this work, we proposed a stretchable photonic crystal-assisted glycoprotein identification approach for early ovarian cancer diagnosis. Stretchable photonic crystals can provide rich optical information to efficiently identify glycoproteins in complex matrices. A double-indicator fluorescence sensor was designed to respond to the protein trunk and oligosaccharide segment of glycoproteins separately for improved recognition accuracy. Seven typical glycoproteins could be discriminated from proteins, saccharides, or mixture interferents. Clinical ovarian cancer samples for early, intermediate, and advanced ovarian cancer and healthy subjects were verified with 100% accuracy. This strategy of stretchable photonic crystal-assisted glycoprotein identification provides an effective method for accurate, rapid ovarian cancer diagnosis and timely clinical treatment.


Asunto(s)
Glicoproteínas , Neoplasias Ováricas , Femenino , Neoplasias Ováricas/diagnóstico , Humanos , Glicoproteínas/análisis , Fotones , Colorantes Fluorescentes/química , Biomarcadores de Tumor/análisis , Cristalización
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