Understanding excipient-induced crystallization of spray-dried amorphous solid dispersion.

This study investigates the compatibility of excipients with the model system SDI-X and their role in the induced crystallization of the amorphous compound-X in tablet formulations. We aimed to establish a straightforward and practical screening approach for evaluating excipient-induced crystallization of SDI in tablet matrices. Three methodologies-binary powder mixture, binary compact, and bilayer tablets-were employed to qualitatively and quantitatively evaluate the recrystallization of SDI-X with various excipients under accelerated storage conditions.

Hydrolysis of cellulose acetate phthalate and hydroxypropyl methylcellulose phthalate in amorphous solid dispersions.

The preparation of amorphous solid dispersions (ASDs) represents a promising strategy for addressing the solubility limitations of poorly soluble drugs, facilitating enhanced oral absorption. Acidic polymers such as cellulose acetate phthalate (CAP) and hydroxypropyl methylcellulose phthalate (HPMCP) have emerged as effective carriers for ASDs. Although the hydrolytic degradation of these polymers has been documented, its impact on the stability of ASDs has not been systematically investigated.

DNA hypomethylation patterns and their impact on the tumor microenvironment in colorectal cancer.

Background: Recent research underscores the pivotal role of immune checkpoints as biomarkers in colorectal cancer (CRC) therapy, highlighting the dynamics of resistance and response to immune checkpoint inhibitors. The impact of epigenetic alterations in CRC, particularly in relation to immune therapy resistance, is not fully understood.

Methods: We integrated a comprehensive dataset encompassing TCGA-COAD, TCGA-READ, and multiple GEO series (GSE14333, GSE37892, GSE41258), along with key epigenetic datasets (TCGA-COAD, TCGA-READ, GSE77718).

The impact of diluents on the compaction, dissolution, and physical stability of amorphous solid dispersion tablets.

Amorphous solid dispersion (ASD) is an effective approach for enhancing the solubility, dissolution, and bioavailability of poorly water-soluble drugs. However, these metastable forms can transform into more thermodynamically stable but less soluble crystalline forms. Despite this challenge, research on processing ASDs into solid dosage forms, such as tablets, is lacking.

Multiomics analyses reveal the mechanisms of the responses of subalpine treeline trees to phenology and winter low-temperature stress.

Withstanding extreme cold stress is a prerequisite for alpine treeline trees to persist and survive. However, the underlying mechanism by which treeline trees sense phenological changes and survive hard winters has not been fully elucidated. Here, we investigated the physiology, transcriptome, and metabolome of the subalpine treeline species Larix chinensis to identify the molecular mechanism of phenological and cold resistance.

Stabilization effects of saccharides in protein formulations: A review of sucrose, trehalose, cyclodextrins and dextrans.

Saccharides are a popular group of stabilizers in liquid, frozen and freeze dried protein formulations. The current work reviewed the stabilization mechanisms of three groups of saccharides: (i) Disaccharides, specifically sucrose and trehalose; (ii) cyclodextrins (CDs), a class of cyclic oligosaccharides; and (iii) dextrans, a class of polysaccharides. Compared to sucrose, trehalose exhibits a more pronounced preferential exclusion effect in liquid protein formulations, due to its stronger interaction with water molecules.

Molecular complexes of drug combinations: A review of cocrystals, salts, coamorphous systems and amorphous solid dispersions.

As the advancements in the medical technology and healthcare develop through the years, combinational therapy has evolved to be an important treatment modality in many disease settings, including cancer, cardiovascular disease and infectious diseases. In an effort to alleviate "pill burden" and improve patient compliance, fixed dose combinations (FDCs) have been developed to be used as effective therapeutics. Among all FDCs, the category of drug-drug molecular complexes has been proven an efficient methodology in designing and treating diseases, with many drugs being approved.

Association between depression status and hearing loss among older adults: The role of outdoor activity engagement.

Background: More than half of Chinese older adults over 60 are suffering from hearing loss, which might increase the risk of depression. Outdoor activity engagement is a key factor to alleviate depression symptoms. This study is conducted to analyze the associations between hearing loss and depression, and explore the role of outdoor activity engagement on depression.

Effects of Additives on the Physical Stability and Dissolution of Polymeric Amorphous Solid Dispersions: a Review.

Polymeric amorphous solid dispersion (ASD) is a popular approach for enhancing the solubility of poorly water-soluble drugs. However, achieving both physical stability and dissolution performance in an ASD prepared with a single polymer can be challenging. Therefore, a secondary excipient can be added.

Construction of the first high-density genetic linkage map and QTL mapping of flavonoid and leaf-size related traits in Epimedium.

Background: Leaves are the main medicinal organ in Epimedium herbs, and leaf flavonoid content is an important criterion of Epimedium herbs. However, the underlying genes that regulate leaf size and flavonoid content are unclear, which limits the use of breeding for Epimedium development. This study focuses on QTL mapping of flavonoid and leaf-size related traits in Epimedium.

Construction of IL-1 signalling pathway correlation model in lung adenocarcinoma and association with immune microenvironment prognosis and immunotherapy: Multi-data validation.

Numerous studies have confirmed the inextricable link between inflammation and malignancy, which is also involved in developing lung adenocarcinoma, where IL-1 signalling is crucial. However, the predictive role of single gene biomarkers is insufficient, and more accurate prognostic models are needed. We downloaded data related to lung adenocarcinoma patients from the GDC, GEO, TISCH2 and TCGA databases for data analysis, model construction and differential gene expression analysis.

Delivery of a therapeutic antibody to the lower gastrointestinal tract for the treatment of infection (CDI).

The colonic delivery system of toxin neutralizing antibody is a promising method for treating infection (CDI) and has some advantages over the parental administration of a neutralizing antibody. However, colonic delivery of biologics presents several challenges, including instability of biologics during encapsulation into the delivery system and harsh conditions in the upper GI tract. In this work, we described a multi-particulate delivery system encapsulating a tetra-valent antibody ABAB-IgG1 with the potential to treat CDI.

Surface Characterization as a Tool for Identifying the Factors Affecting the Dissolution Rate of Amorphous Solid Dispersion Tablets.

An amorphous solid dispersion (ASD) is a commonly used approach to enhancing the dissolution of poorly aqueous soluble drugs. Selecting the desired polymer and drug loading can be time-consuming. Surface properties, such as surface composition and wetting behavior, are essential factors controlling the dissolution of ASD tablets.

Evaluation of Alternative Metallic Stearates as Lubricants in Pharmaceutical Tablet Formulation.

Magnesium stearate (MgSt) is perhaps one of the most frequently used lubricants in tablet formulation due to its superior lubrication capacity, yet it could also negatively affect the critical quality attributes of pharmaceutical products. Therefore, we provided a rather comprehensive evaluation of another two FDA-approved metallic stearates, sodium stearate (NaSt) and calcium stearate (CaSt), as alternative tablet lubricants. The primary objective of the present study is to comparatively evaluate the physicochemical properties and lubrication efficiency of the three metallic stearates.

Cholecalciferol complexation with hydroxypropyl-β-cyclodextrin (HPBCD) and its molecular dynamics simulation.

The focus of the current study is to investigate cholecalciferol (vitamin D3) solubilization by hydroxypropyl-β-cyclodextrin (HPBCD) complexation through experimental and computational studies. Phase solubility diagram of vitamin D3 (completely insoluble in water) has an A profile revealing a deviation from a linear regression with HPBCD concentration increase. Differential scanning calorimetry (DSC) is the best tool to confirm complex formation by disappearance of cholecalciferol exothermic peak in cholecalciferol-HPBCD complex thermogram, due to its amorphous state by entering HPBCD inner hydrophobic cavity, similarly validated by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD).

C-terminal-mediated homodimerization of Expanded is critical for its ability to promote Hippo signalling in Drosophila.

Hippo signalling plays key role in tissue growth and homeostasis, and its dysregulation is implicated in various human diseases. Expanded (Ex) is an important upstream activator of Hippo signalling; however, how Ex activates Hippo signalling is still poorly understood. Here, we demonstrate that Ex forms a homodimer via C-terminal interaction, and that the ExC2 region (912-1164 aa) is sufficient and essential for Ex dimerization.

Role of polymers in the physical and chemical stability of amorphous solid dispersion: A case study of carbamazepine.

Incorporating the amorphous drug in polymeric components has been demonstrated as a feasible approach to enhance the bioavailability of poorly water-soluble drugs. The objective of this study was to investigate the role of polymers in the stability of amorphous solid dispersion (ASD) by evaluating the drug-polymer interaction, microenvironmental pH, and stability of ASD. Carbamazepine (CBZ), a Biopharmaceutics Classification System Class II compound, was utilized as a model drug.

Spray layering of human immunoglobulin G: Optimization of formulation and process parameters.

Spray layering is a technique used to apply drug or functional polymers onto carrier beads; in addition, it can be used as an alternative method for protein drying and to layer protein on a multiparticulate delivery system. In this study, the effects of formulation variables and process parameters on human immunoglobulin G (IgG) properties during spray layering were studied. Excipients including polyvinylpyrrolidone (PVP), trehalose, sucrose, L-arginine monohydrochloride were studied for their effects on improving IgG stability during spray layering.

Evaluation of tableting performance of Poly (ethylene oxide) in abuse-deterrent formulations using compaction simulation studies.

Poly (ethylene oxide) (PEO) has been widely used in abuse-deterrent formulations (ADFs) to increase tablet hardness. Previous studies have shown that formulation variables such as processing conditions and particle size of PEO can affect ADF performance in drug extraction efficiency. This work aims to understand the effect of PEO grades and sources on the compaction characteristics of model ADFs.

Prioritized carbon allocation to storage of different functional types of species at the upper range limits is driven by different environmental drivers.

The upper elevational range limit of tree species (including treeline and non-treeline species) is generally considered to result from either carbon limitation or sink limitation. Some evidence also suggests that tree line might reflect preferential carbon allocation to NSC storage at the expense of growth. How might the importance of these potential mechanisms be determined? We used an elevational gradient to examine light-saturated photosynthesis (Asat) and NSC concentrations in plant tissues of three different functional types of tree species.

Polymorphisms of four candidate genes and their correlations with growth traits in blue fox (Alopex lagopus).

To improve the accuracy and genetic progress of blue fox breeding, the relationships between genetic polymorphisms and growth and reproductive traits of the blue fox were investigated. MC4R, MC3R, INHA and INHBA were selected as candidate genes for molecular evolution and statistical analyses. Single-factor variance analyses showed that the MC4R (g.

Characterization of Dopaminergic System in the Striatum of Young Adult Park2 Knockout Rats.

Mutations in parkin gene (Park2) are linked to early-onset autosomal recessive Parkinson's disease (PD) and young-onset sporadic PD. Park2 knockout (PKO) rodents; however, do not display neurodegeneration of the nigrostriatal pathway, suggesting age-dependent compensatory changes. Our goal was to examine dopaminergic (DAergic) system in the striatum of 2 month-old PKO rats in order to characterize compensatory mechanisms that may have occurred within the system.

The impact of microfluidic mixing of triblock micelleplexes on in vitro / in vivo gene silencing and intracellular trafficking.

The triblock copolymer polyethylenimine-polycaprolactone-polyethylene glycol (PEI-PCL-PEG) has been shown to spontaneously assemble into nano-sized particulate carriers capable of complexing with nucleic acids for gene delivery. The objective of this study was to investigate micelleplex characteristics, their in vitro and in vivo fate following microfluidic preparation of siRNA nanoparticles compared to the routinely used batch reactor mixing technique. Herein, PEI-PCL-PEG nanoparticles were prepared with batch reactor or microfluidic mixing techniques and characterized by various biochemical assays and in cell culture.

Neurotoxic Doses of Chronic Methamphetamine Trigger Retrotransposition of the Identifier Element in Rat Dorsal Dentate Gyrus.

Short interspersed elements (SINEs) are typically silenced by DNA hypermethylation in somatic cells, but can retrotranspose in proliferating cells during adult neurogenesis. Hypomethylation caused by disease pathology or genotoxic stress leads to genomic instability of SINEs. The goal of the present investigation was to determine whether neurotoxic doses of binge or chronic methamphetamine (METH) trigger retrotransposition of the identifier (ID) element, a member of the rat SINE family, in the dentate gyrus genomic DNA.