This study investigates the interrelationships among drug loading, steric hindrance (Sh), defined as the spatial constraints imposed by the crystallized polymer network that physically restrict drug crystal growth, effective glass transition temperature (Tgᴱ), and drug particle size in crystalline solid dispersion (CSD) systems. Furthermore, we examine how CSD formulations enhance dissolution rates, oral bioavailability, and anti-liver cancer efficacy through comprehensive in vitro and in vivo studies. SOR-P188-CSD with different drug loadings were synthesized via spray drying, utilizing Sorafenib (SOR) as the model drug and poloxamer 188 (P188) as the carrier. The association between Sh/TgE, drug particle size, and dissolution behavior of CSDs was investigated by probing the crystalline domain (particle size), crystallization kinetics, and interaction dynamics within the CSD matrices. Notably, the particle size of SOR within SOR-P188-CSD exhibited a significant reduction compared to the pure drug. Analysis of crystallization kinetics unveiled a two-step crystallization mechanism for SOR-P188-CSD, where P188 crystallization preceded that of SOR. Intriguingly, an intermolecular interaction between SOR and P188 was observed, exerting an inhibitory effect on the crystallization kinetics of both components. This inhibitory effect escalated concomitantly with increasing drug loading. Within the SOR-P188-CSD system, P188 within formulations featuring low drug loading orchestrated a reduction in drug particle size by modulating the transverse and longitudinal growth rates of SOR, with Sh serving as the primary influencing factor. Conversely, in formulations with high drug loading, TgE of CSD interacted with temperature to regulate crystal nucleation and growth rates, thereby reducing drug particle size, with TgE emerging as the principal influencing factor. Subsequent in vitro and in vivo dissolution studies demonstrated a marked enhancement in the dissolution rate and bioavailability of drugs encapsulated within SOR-P188-CSD formulations compared to the active pharmaceutical ingredient (API). In the nude mouse liver cancer xenograft model, SOR-P188-CSD can significantly inhibit tumor growth by suppressing the expression of angiogenesis related factors (CD31, CD34, VEGF), tumor proliferation related factors (Ki67), and iron death related protein (GPX4). Collectively, our findings underscore the pivotal role of Sh/TgE in modulating drug particle size within CSD matrices through distinct mechanisms. Furthermore, our study underscores the potential of P188-mediated CSD formulations in augmenting the dissolution rate and bioavailability of poorly soluble drugs by minimizing drug particle size and sustaining drug supersaturation, thereby enhancing the efficacy of sorafenib in treating liver cancer.

Glycosidases are key enzymes involved in carbohydrate metabolism. Members of the GH3 family have emerged as therapeutic targets due to their roles in natural product biosynthesis and disease. Transition-state analogues represent a powerful strategy for glycosidase inhibition, and exoglycals (C-glycosylidenes) have gained interest as conformational mimics of glycosidic bond hydrolysis. Herein, we report the synthesis of novel exoglycals bearing diverse substituents, including terminal alkynes and thymidyl residues, via a modified Julia-olefination strategy from sugar-derived lactones and substituted sulfones. Selected alkyne-containing exoglycals were further functionalized through cycloaddition with azidothymidine. Inhibition studies against EryBI, a GH3 glycosyl hydrolase, were performed. Kinetic analysis revealed diverse inhibitory mechanisms among the exoglycals, displaying competitive inhibition, with Ki values spanning micromolar to millimolar affinities. To contextualize the inhibitory potential of exoglycals, we evaluated three clinically relevant macrolide antibiotics-erythromycin, clarithromycin, and azithromycin. Intriguingly, these macrolides exhibited competitive or uncompetitive inhibition, contrasting with the consistent competitive behavior of exoglycals. This comparative analysis highlights the scaffold-dependent selectivity of GH3 inhibition. Our results demonstrate exoglycals as tunable scaffolds for glycosidase inhibition of GH3 glycosidases and provide mechanistic distinctions between carbohydrate mimics and macrolide antibiotics. These insights could guide the development of next-generation glycosidase inhibitors with improved specificity.

In recent years, researchers have focused on developing innovative biochar modification techniques to enhance adsorption efficiency and reduce the mobility and bioavailability of heavy metals. However, few studies have investigated the application of modified biochar in heavy metals-contaminated soils, with most research focusing on aqueous solutions. In Iran, the potential of biochar as an effective adsorbent for removing heavy metals from contaminated soils, especially acidic soils, has been largely overlooked. The effectiveness of biochar is influenced by both the type of biomass used and the method of modification. Additionally, there is a significant gap in current literature regarding the research on thiourea as a potential modification agent for biochar. This study focused on the characteristics of thiourea-modified wheat straw biochar (TWB) and its effects on the adsorption isotherms and kinetics of heavy metals (Cd, Ni, and Zn) in acidic soil. The biochar was produced from wheat straw in an oxygen-free furnace at a temperature of 550 °C for 3 h, with a heating rate of 25 °C per min. To enhance the adsorption efficiency, thiourea was used to modify the wheat straw biochar (WB). The findings revealed that the thiourea modification reduced the carbon content but increased the nitrogen, hydrogen, sulfur, oxygen levels, specific surface area, cation exchange capacity (CEC), and pH compared to unmodified biochar. Adsorption isotherms and kinetics analyses indicated that the Langmuir model best described the adsorption of heavy metals in soil treated with both TWB and WB, while the pseudo-second-order model more accurately represented the adsorption kinetics. The results indicated that the adsorption of Cd, Ni, and Zn in soil treated with 8% TWB was significantly higher than in the control, achieving levels of 6164.45, 4684.47, and 4233.58 mg kg-1, respectively. This study demonstrated that TWB enhances the adsorption of heavy metals due to its advantageous properties, which include an optimal pH, high CEC, a variety of functional groups, a large specific surface area, and a porous structure. Therefore, thiourea-modified wheat straw biochar serves as an effective, economical, and environmentally friendly adsorbent for immobilizing heavy metals and reducing their bioavailability in acidic contaminated soils.

Investigating the synergy of fast co-pyrolysis of spent coffee ground and disposed urban facemask: analysis of kinetics and product compositions

Defect-rich phosphorus-doped 3D carbon cathodes with graphitic domains for high-performance zinc-ion storage devices.

From garlic proteins to bioactive peptides: A computer-aided screening for saltiness-enhancers and angiotensin I-converting enzyme inhibitors with mechanistic and kinetic analysis.

Efficient recovery of vanadium from calcified vanadium slag by reductive leaching-selective precipitation: Thermodynamic and kinetic analysis and mechanism investigation

Excellent catalytic activity of in-situ formed Ti3C2 nanoparticles for boosting hydrogen release from light metal hydride.

Rapid kinase activity detection and kinetic analysis using a convenient EGFR FRET-based detection probe.

Long-term prediction of radiation-induced optic neuropathy: A mixed-effects analysis of visual field kinetics following proton therapy.

Photocatalytic adsorption-driven removal of rhodamine B by silver Tetratungstate-modified bentonite: Kinetic, isotherm, and thermodynamic analysis

Functional characterization of loganic acid O-methyltransferase and secologanin synthase from Uncaria rhynchophylla and two-step biosynthesis of secologanin in tobacco.

A comprehensive study of CO2 capture using attapulgite and novel hybrid Attapulgite/13X zeolite composite: kinetic, isotherm, and thermodynamic analysis

Kinetic, thermodynamic, and reaction mechanism analysis of apple pomace (Malus Domestica Borkh) for bioenergy potential using single and multi-step (Deconvolution) approaches

Emerging adsorbent systems for sugar-derived contaminants removal: Sustainable strategies for sugar processing wastewater remediation.

Cooperativity between endogenous glutamylcysteinylglycine-based oligopeptides and drugs determines the function of the multidrug transporter ABCC1.

Co-pyrolysis of garlic (Allium sativum L.) straw and polyethylene waste through thermogravimetric analysis: Assessing synergistic effects in terms of kinetic and thermodynamic analyses.

Kinetic analysis of dye reduction profiles provide deeper insights into the electron transfer activity of bacterial cultures.

Targeted screening of pancreatic lipase inhibitory peptides from quinoa protein hydrolysates by ligand fishing.

A new analytical expression based on the one trap one recombination model to describe thermally assisted optically stimulated luminescence decay curves; simulation results and thermal assistance study.