Solubility Profile Research Articles

PHARMACEUTICAL NANOCRYSTALS: AN EXTENSIVE OVERVIEW

In pharmaceutical development, pharmaceutical nanocrystals sized between 10 and 1000 nanometers have been found to hold promise in improving drug solubility. Since they comprise only the active pharmaceutical ingredient, nanocrystals have dramatically increased surface area-to-volume ratios, ensuring improved in vitro dissolution and solubility profiles. In view of their strengths and limitations, different production strategies have been reviewed: methods of size reduction such as wet milling and high-pressure homogenization; the bottom-up approaches of controlled precipitation and supercritical fluid technology; and efficient ways to stabilize nanocrystal formulations aided by excipients like surfactants and polymers. Techniques used in this characterization of nanocrystals include size analysis, surface-charge measurement, and assessment of crystalline structure. The routes of administration, such as oral, injectable, inhaled, and topical application, are reviewed alongside commercially successful products and clinical trials. This work reviews dynamic regulatory scenarios and current challenges of large-scale production, long-term stability, and nanotoxicity evaluation. In addition, it addresses the emerging trends in nanocrystal technology in the field of personalized medicine, targeted drug delivery, and theranostic approaches associated with how nanocrystals can help optimize the outcome of a patient in drug delivery systems.

Unveiling the potent Antimicrobial Photodynamic Therapy in Gram-positive and Gram-negative bacteria – Water remediation with monocharged chlorins

Water pollution is a significant concern worldwide, and it includes contaminants such as antibiotic-resistant pathogens. Antimicrobial photodynamic therapy (aPDT) offers a non-invasive and non-toxic alternative for the inactivation of these microorganisms. So, this study reports the synthesis, structural characterisation, photophysical properties, and aPDT efficacy of cationic free-base and zinc(II) chlorin (Chl) derivatives bearing N,N-dimethylpyrrolydinium groups (H2Chl 1a and ZnChl 1b). The aPDT assays were performed against two bacterial models: Staphylococcus aureus (Gram-(+)) and Escherichia coli (Gram-(–)). The H2Chl 1a and ZnChl 1b distinct’s solubility profile, coupled with their ability to generate singlet oxygen (1O2) under light exposure, (H2Chl 1a, ФΔ = 0.58 <TPP, ФΔ = 0.65 < ZnChl 1b, ФΔ = 0.83) opens up their potential application as photosensitizers (PS) in aPDT. The effectiveness of H2Chl 1a and ZnChl 1b at 1.0 and 5.0 μM in aPDT against S. aureus and E. coli at 500 W.m–2 (total exposure time: 60 –120 min) showed a viability reduction > 6.0 log10 CFU.mL–1. Additionally, KI was used as a coadjuvant to potentiate the photoinactivation of E. coli, reaching the method’s detection limit (> 4.0 log10 RLU). As most of the PS developed to inactivate Gram-negative bacteria are cationic with three or more charges, the fact that the H2Chl 1a and ZnChl 1b with only one cationic charge photoinactivate E. coli at low concentrations and with a reduced light dose, it is an importing discovery that deserves further exploration. These monocharged chlorin dyes have the potential for water remediation.

Functionalisation of chitosan with methacryloyl and crotonoyl groups as a strategy to enhance its mucoadhesive properties

Mucoadhesive polymers are crucial for prolonging drug retention on mucosal surfaces. This study focuses on synthesising and characterising novel derivatives by reacting chitosan with crotonic and methacrylic anhydrides. The structure of the resulting derivatives was confirmed using proton-nuclear magnetic resonance spectroscopy and Fourier-transform infrared spectroscopy. It was established that the degree of substitution plays a crucial role in the pH-dependent solubility profiles and electrophoretic mobility of the chitosan derivatives. Spray-drying chitosan solutions enabled preparation of microparticles, whose mucoadhesive properties were evaluated using fluorescence flow-through studies and tensile test, demonstrating improved retention on sheep nasal mucosa for modified derivatives. Acute toxicity studies conducted in vivo using planaria and in vitro using MTT assay with the Caco-2 cell line, a model of the mucosal epithelium in vitro, showed that the novel derivatives are not cytotoxic. These findings emphasise the potential of tailored chitosan chemical modifications for enhancing transmucosal drug delivery.

Enhancing Ketoprofen Solubility: A Strategic Approach Using Solid Dispersion and Response Surface Methodology.

In the pharmaceutical sciences, the solubility profile of therapeutic molecules is crucial for identifying and formulating drugs and evaluating their quality across the drug discovery pipeline based on factors like oral bioavailability, metabolic transformation, biodistribution kinetics, and potential toxicological implications. The investigation aims to enhance the solubility parameters of ketoprofen (BCS-II class), which exhibits low solubility and high permeability. In this method, hydrotrope blends of aromatic sodium benzoate and electrolyte sodium acetate were employed to enhance the solubility parameter of ketoprofen. Several batches of solid dispersion of ketoprofen were made using a solvent evaporation method, and the response surface method 3² factorial design was used to find the best one. The optimised formulation, KSD9, underwent in-vitro drug dissolution, DSC, pXRD, and SEM studies. The optimized batch demonstrated substantial improvement in ketoprofen solubility, attributed to mixed hydrotropy. The results indicated that both solubility and %CDR improved when hydrotropes were employed, suggesting a direct proportionality between the rise in solubility and %CDR. Formulations KSD1-KSD9 exhibited solubility enhancements ranging from 2.23 to 5.77-fold, along with an elevation in %CDR from 72.28% to 94.76%. This implies that the %CDR was modulated by the hydrotropes, specifically influenced by the concentration levels of the independent variables. An increase in hydrotrope levels corresponded to an increase in %CDR. The positive coefficients in the quadratic equation for %CDR underscored the significant role of these independent variables in augmenting the in-vitro release of Ketoprofen. Similarly, during a comparative dissolution investigation, the optimized KSD9 formulation exhibited remarkable solubility and drug content compared to conventional Ketoprofen dispersible tablets. The synergistic effect of combining two hydrotropic agents significantly increased the solubility of ketoprofen by up to 58 times. The results indicated that the independent variables exerted a positive influence on solubility and %CDR. Furthermore, the responses were contingent on the specific hydrotropes selected, which functioned as the independent variables. Analyzing the r² and ANOVA results suggested that the dependent variables aligned well with the chosen model. Visual representations, such as the 3D response surface plot and contour plot, demonstrated the impact of each hydrotrope individually and when combined. Overall, employing hydrotropes led to improved solubility and %CDR, highlighting a direct proportionality between the rise in solubility and %CDR. Mixed hydrotropic lessens the toxicity associated with individual hydrotrope concentrations while also offering a sustainable and eco-friendly alternative. This study paves the way for future research aiming to improve the solubility of low- solubility drugs, broadening their clinical applications.

Enhanced Solubility and Flavour Profile of Instant Date Seeds (Phoenix dactylifera L.) Coffee as Caffeine-Free Beverage

Enhanced Solubility and Flavour Profile of Instant Date Seeds (Phoenix dactylifera L.) Coffee as Caffeine-Free Beverage

Three-Dimensional Model Analysis Revealed Differential Cytotoxic Effects of the NK-92 Cell Line and Primary NK Cells on Breast and Ovarian Carcinoma Cell Lines Mediated by Variations in Receptor-Ligand Interactions and Soluble Factor Profiles.

Background/objectives: The functional activity of a certain tumor determines the effectiveness of primary NK cells and NK-92 cell line-based cancer therapy; their therapeutic effectiveness against different tumors can vary. This work provides a direct simultaneous comparison of the cytotoxic effects of in vitro-activated peripheral NK (pNK) cells and NK-92 cells in spheroid models of BT-474, MCF7 and SKOV-3 carcinomas and uncovers the reasons for the differential effectiveness of NK cells against tumors. Methods: Tumor spheroids of similar size and shape, obtained from agarose molds, were incubated with NK-92 or pNK cells for 24 h. Tumor cell death was detected using flow cytometry or confocal microscopy. Cytokine production, granzyme B levels and NK cell degranulation analyses were performed, along with pNK and target-cell phenotypic characterization. Results: While NK-92 and pNK cells lysed BT-474 spheroids with comparably low efficiency, pNK cells were more capable of eliminating MCF7 and SKOV-3 spheroids than NK-92 cells were. The results of the functional and phenotypic analyses strongly support the participation of the NKG2D-NKG2DL pathway in pNK cell activation induced by the most sensitive cytotoxic attack on SKOV-3 spheroids, whereas the CX3CR1-CX3CL1 axis appears to be involved in the pNK reaction against MCF-7 spheroids. Conclusions: We provide a new approach for the preliminary identification of the most promising NK cell receptors that can alter the effectiveness of cancer therapy depending on the specific tumor type. Using this approach, NK-92 cells or pNK subsets can be selected for further accumulation and/or genetic modification to improve specificity and reactivity.

Effect of spray-drying or fermentation on the solubility and carbohydrate profile of chickpea hydrolysates for beverage formulation

Powder beverage bases were developed using extruded and hydrolyzed chickpea supernatant through freeze-drying. This study evaluated the effects of spray-drying and adjuvant incorporation for producing powders and supernatant fermentation with LAB strains prior freeze-drying on the carbohydrate composition, structural integrity, and physical properties of chickpea beverage base powders. All powders had low insoluble (<0.2%) and soluble (<3%) dietary fiber contents due to processing. Starch content decreased below 9.49% when using adjuvants and 10.61% during fermentation. Both treatments also reduce raffinose oligosaccharide content below 6.1 mM/100 g. Spray-drying and adjuvant addition promoted a more amorphous starch structure, enhancing solubility, while fermentation induced more crystallinity, according to FTIR data. Microscopy showed small particle clusters and lack of birefringence. SEM images revealed starch granule damage from both fermentation and spray-drying, with more uniform particles in spray-dried powders. Spray-drying resulted in the smallest particle sizes (455-457 nm) and higher absolute zeta potential (8.12-9.51), indicating greater stability. Fermentation had the opposite effect, negatively impacting the colloidal system stability. Samples had a pH close to 6, except fermented powders with a pH of 3.6, affecting colloidal stability. Fermentation significantly reduced solubility but without practical implications, as all samples had solubility values over 93%, which is desirable for beverage-based powders. Spray-drying and fermentation altered the carbohydrate profile and structure of the powders. Fermentation prior producing powders may provide benefits, but it slightly decreases the system stability. Spray-drying can be used instead of freeze-drying to produce stable chickpea base powders that are highly soluble.

Association between aortic calcification and cytokine levels in patients with peripheral artery disease.

Aortic calcification-a marker of advanced atherosclerosis in large arteries-associates with cardiovascular mortality and morbidity. Little is known about the soluble inflamJarmatory profiles involved in large artery atherosclerosis. We investigated the correlation between aortic calcification in the abdominal aorta and cytokine levels in a cohort of peripheral artery disease patients. Aortic calcification index was measured from computed tomography exams and circulating cytokine levels were analyzed from blood serum samples of 156 consecutive patients prior to invasive treatment of peripheral artery disease. The study included 156 patients (mean age 70.7 years, 64 (41.0%) women). The mean ankle-brachial index (ABI) was 0.64 and the mean aortic calcification index (ACI) was 52.3. ACI was associated with cytokines cutaneous T-cell-attracting chemokine CTACK (β 23.08, SE 5.22, p < 0.001) and monokine induced by gamma-interferon MIG (β 9.40, SE 2.82, p 0.001) in univariate linear regression. After adjustment with cardiovascular risk factors, CTACK and MIG were independently associated with ACI, β 17.9 (SE 5.22, p < 0.001) for CTACK and β 6.80 (SE 3.33, p 0.043) for MIG. CTACK was significantly higher in the patients representing the highest ACI tertile (highest vs. middle, 7.53 vs. 7.34 Tukeys HSD p-value 0.023 and highest vs. lowest tertile 7.53 vs. 7.29, Tukeys HSD p-value 0.002). MIG was significantly higher in the highest tertile versus lowest (7.65 vs. 7.30, Tukeys HSD p-value 0.027). Cytokines CTACK and MIG are associated with higher ACI, suggesting that CTACK and MIG reflect atherosclerotic disease burden of the aorta. This might further suggest the possible association with other cardiovascular morbidities.

Proteomic Profiles of Maternal Plasma Extracellular Vesicles for Prediction of Preeclampsia.

Preeclampsia is a heterogeneous syndrome of diverse etiologies and molecular pathways leading to distinct clinical subtypes. Herein, we aimed to characterize the extracellular vesicle (EV)-associated and soluble fractions of the maternal plasma proteome in patients with preeclampsia and to assess their value for disease prediction. This case-control study included 24 women with term preeclampsia, 23 women with preterm preeclampsia, and 94 healthy pregnant controls. Blood samples were collected from cases on average 7 weeks before the diagnosis of preeclampsia and were matched to control samples. Soluble and EV fractions were separated from maternal plasma; EVs were confirmed by cryo-EM, NanoSight, and flow cytometry; and 82 proteins were analyzed with bead-based, multiplexed immunoassays. Quantile regression analysis and random forest models were implemented to evaluate protein concentration differences and their predictive accuracy. Preeclampsia subgroups defined by molecular profiles were identified by hierarchical cluster analysis. Significance was set at p < 0.05 or false discovery rate-adjusted q < 0.1. In preterm preeclampsia, PlGF, PTX3, and VEGFR-1 displayed differential abundance in both soluble and EV fractions, whereas angiogenin, CD40L, endoglin, galectin-1, IL-27, CCL19, and TIMP1 were changed only in the soluble fraction (q < 0.1). The direction of changes in the EV fraction was consistent with that in the soluble fraction for nine proteins. In term preeclampsia, CCL3 had increased abundance in both fractions (q < 0.1). The combined EV and soluble fraction proteomic profiles predicted preterm and term preeclampsia with an AUC of 78% (95% CI, 66%-90%) and 68% (95% CI, 56%-80%), respectively. Three clusters of preeclampsia featuring distinct clinical characteristics and placental pathology were identified based on combined protein data. Our findings reveal distinct alterations of the maternal EV-associated and soluble plasma proteome in preterm and term preeclampsia and identify molecular subgroups of patients with distinct clinical and placental histopathologic features.

Preformulation Studies of Pitavastatin Calcium– A Primary Step in Further Design of Chronotherapeutic Formulation Synchronized with Circadian Rhythm.

The principal goal and objective of this present research work were to perform a preformulation analysis of Pitavastatin calcium to produce a further stable, efficient chroomodulated drug delivery system. Pitavastatin calcium was analyzed to study its micrometric properties, equilibrium solubility profile in different media, and determination of purity by subjecting to fouriertransform infrared spectroscopy (FTIR) studies, by determining the absorption maxima in the medium along with differential scanning Calorimetry- DSC. Spectral analysis of UV studies and calibration curve plotting was done for further analytical research. The melting point was analyzed, and PXRD studies were conducted to identify the crystallinity. The Pitavastatin calcium micromeritic properties were found to be good with bulk density- 0.408 g/mL, tapped density 0.476 g/mL, Carr’s index 14.2%, Hausner’s ratio 1.16 with 32.0050 angle of repose. The equilibrium solubility study indicates drug has peak solubility in media 0.1 N Hcl and reduced solubility in distilled water. The infrared spectrum indicated peaks corresponding to functional groups conforming to the purity. The UV spectrum exhibited absorption maxima at 250 nm in media 0.1N HCl and 245 in pH phosphate buffer 6.8 and in all other mediums, which is the same as the standard literature indication. The calibration curve exhibited linearity in accordance with Beer Lambert’s law. The PXRD studies produced 2θ values corresponding to pitavastatin calcium as per literature conforming to the crystallinity. The Preformulation analysis concludes that the drug was pure pitavastatin calcium with corresponding absorption maxima, an infrared spectral functional group with crystallinity. It specifies that the drug mandates the improvement of solubility for further formulation development.

Distinct soluble immune checkpoint profiles characterize COVID-19 severity, mortality and SARS-CoV-2 variant infections.

Over the past four years, the COVID-19 pandemic has posed serious global health challenges. The severe form of disease and death resulted from the failure of immune regulatory mechanisms, closely highlighted by the dual proinflammatory cytokine and soluble immune checkpoint (sICP) storm. Identifying the individual factors impacting on disease severity, evolution and outcome, as well as any additional interconnections, have become of high scientific interest. In this study, we evaluated a novel panel composed of ten sICPs for the predictive values of COVID-19 disease severity, mortality and Delta vs. Omicron variant infections in relation to hyperinflammatory biomarkers. The serum levels of sICPs from confirmed SARS-CoV-2 infected patients at hospital admission were determined by Luminex, and artificial neural network analysis was applied for defining the distinct patterns of molecular associations with each form of disease: mild, moderate, and severe. Notably, distinct sICP profiles characterized various stages of disease and Delta infections: while sCD40 played a central role in all defined diagrams, the differences emerged from the distribution levels of four molecules recently found and relatively less investigated (sCD30, s4-1BB, sTIM-1, sB7-H3), and their associations with various hematological and biochemical inflammatory biomarkers. The artificial neural network analysis revealed the prominent role of serum sTIM-1 and Galectin-9 levels at hospital admission in discriminating between survivors and non-survivors, as well as the role of specific anti-interleukin therapy (Tocilizumab, Anakinra) in improving survival for patients with initially high sTIM-1 levels. Furthermore, strong associations between sCD40 and Galectin-9 with suPAR defined the Omicron variant infections, while the positive match of sCD40 with sTREM-1 serum levels characterized the Delta-infected patients. Of importance, this study provides a comprehensive analysis of circulatory immune factors governing the COVID-19 pathology, and identifies key roles of sCD40, sTIM-1, and Galectin-9 in predicting mortality.

Synthesis, cytotoxic evaluation, and in silico studies of novel benzenesulfonamide-thiazolidinone derivatives against colorectal carcinoma

Thirteen new benzenesulfonamide derivatives containing 4-thiazolidinone were synthesized. Their cytotoxic properties were tested on colorectal carcinoma (HT-29, DLD-1, COLO-205) and normal colon fibroblast (CCD-986Sk) cell lines. Compounds 3l (IC50=114.62 µM), 3a (IC50=25.82 µM), 3k (IC50=30.99 µM), and 3i (IC50=62.94 µM) showed the highest cytotoxicity on HT-29, DLD-1, COLO-205, and CCD-986Sk cell lines, respectively. Compound 3e (IC50=1075.4 µM) exhibited the least cytotoxicity against CCD-986Sk. The apoptosis profile of 5-FU at 5 µM was similar to that of compound 3e at 30 µM. Molecular docking and MD simulations showed stable interactions for compounds 3i and 3e. Molecular docking and MD simulations revealed that compounds 3i and 3e exhibit stable interactions with key cancer-related protein targets, particularly TGFβ2. These interactions suggest their potential as therapeutic agents. The predicted ADME parameters further highlighted compounds 3e and 3i for their favorable lipophilicity, solubility, permeability, and oral absorption profiles, supporting their promise as candidates for future drug development.

Variation and Abundance of Resistant Starch in Selected Banana Cultivars in Uganda.

The physiochemical, structural, and molecular characteristics of starch influence its functional properties, thereby dictating its utilization. The study aimed to profile the properties and quantity of resistant starch (RS) from 15 different banana varieties, extracted using a combination of alkaline and enzyme treatments. Granular structure and molecular organization were analyzed using light microscopy, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The physiochemical and functional properties were also investigated. RS content ranged from 49% to 80% without significant relationship to amylose (AM) (r = -0.1062). SEM revealed significant microarchitectural differences on the granules potentially affecting granule digestibility. FTIR and chemometrics identified differences in the crystalline peaks, yielding varying degrees of the molecular order of the RS polymers that aid in differentiating the RS sources. Despite similar solubility and swelling profiles, the pasting profiles varied across varieties, indicating high paste stability in hydrothermal processing. Clarity ranged from 43% to 93%, attributed to amylose leaching. This study highlights that RS from bananas varies in quantity, structure, and functionality, necessitating individualized approaches for processing and utilization.

Formulation and &amp;lt;i&amp;gt;in vitro&amp;lt;/i&amp;gt; Evaluation of Liquisolid Compact of Celecoxib

&amp;lt;i&amp;gt;Introduction&amp;lt;/i&amp;gt;: The liquisolid technique presents a promising avenue for enhancing the dissolution rate and bioavailability of poorly water-soluble drugs like celecoxib. This study investigated the formulation and evaluation of celecoxib tablets using this technique. &amp;lt;i&amp;gt;Aim&amp;lt;/i&amp;gt;: To formulate and evaluate celecoxib tablets using the liquisolid technique, with the objective of enhancing its dissolution rate and bioavailability. &amp;lt;i&amp;gt;Methods&amp;lt;/i&amp;gt;: Celecoxib tablets were prepared using the liquid-solid technique by incorporating a non-volatile liquid medication carrier and a suitable solid carrier. Various formulations were developed by altering the ratios of drug, carrier, and coating materials. The prepared tablets were characterized for their physical properties, drug content uniformity, &amp;lt;i&amp;gt;in vitro&amp;lt;/i&amp;gt; dissolution behavior, and compatibility using Fourier-transform infrared (FTIR) spectroscopy. &amp;lt;i&amp;gt;Results&amp;lt;/i&amp;gt;: The solubility profile showed that the maximum rate of solubility was recorded in PEG-400 (11.03 ± 0.01) when compared to other non-volatile solvents. The angle of slide, indicated that the excipients used were within the acceptable limit of 33°. The FTIR spectroscopy showed compatibility of the drug and excipients. The results of the SEM showed that spherically-shaped vesicles were formed. Evaluation of the pre-compression parameters indicated that the drug content was highest in batch F-11 hence its optimization (96.1 ± 0.90). The post compression evaluation indicated that the official tests were within the acceptable range for disintegration time (2.25 ± 0.35). The results of the &amp;lt;i&amp;gt;in vitro&amp;lt;/i&amp;gt; release studies of the optimized formulation, conventional tablet and reference commercial tablet showed that the amount of drug released increased steadily with time over the 1-hour period. &amp;lt;i&amp;gt;Conclusion&amp;lt;/i&amp;gt;: Our findings underscore its viability as a strategy to enhance the therapeutic efficacy of poorly water-soluble drugs, offering promising prospects for pharmaceutical formulation.

GC-MS profiling of the leaf extract of Garcinia pedunculata, molecular docking, ADME/drug likeness predictions and toxicity analysis

Medicinal plants have long been valued for their efficacy, cultural acceptance and lower side effects. Amidst rising concerns about multidrug-resistant bacteria, there is an increasing push to identify novel plant-based drugs with unique mechanisms of action. Garcinia pedunculata, commonly used as food and traditional medicine among tribal communities in North Eastern India, was investigated for its potential medicinal properties. The study involved analyzing the phytoconstituents of the methanolic leaf extract using GC-MS (Gas Chromatography- Mass Spectrometry), which identified 30 compounds. These compounds were further evaluated through in silico studies, including drug-likeness assessments and molecular docking. Molecular docking results indicated that the compounds strongly interacted with Penicillin Binding Protein 4 (PBP4) of Staphylococcus aureus (S aureus), a well-known drug target. Notably, ethane-1,1-diol dipropanoate demonstrated favorable drug-like properties, meeting four out of five drug filters and exhibiting promising physiochemical characteristics, lipophilicity, solubility and pharmacokinetic profiles with minimal toxicity. This suggests its potential for development into novel antimicrobial formulations. Further research using animal models is underway to validate these findings in vivo.

Salmonella pathogenesis-based In-silico design and immunoinformatic analysis of multi-epitope vaccine constructs in broiler veterinary medicine

Salmonellosis, a zoonotic gastrointestinal disease, presents a significant global health burden with a high incidence rate. Transmission primarily occurs through the consumption of contaminated poultry products, although water and contact with asymptomatic animals are also vectors. The disease’s pervasiveness has prompted international health organizations to advocate for robust prevention and control strategies. This study focuses on the in-silico design of a multi-epitope vaccine targeting Salmonella enterica serovar Typhimurium’s fimH protein, a fimbriae component crucial for bacterial adhesion and pathogenicity. The vaccine construct was developed by identifying and synthesizing non-allergenic, antigenic, and non-toxic epitopes for both Cytotoxic T Lymphocytes and Helper T Lymphocytes. Adjuvants were incorporated to enhance immunogenicity, and the vaccine’s structure was modeled using advanced bioinformatics tools. The proposed vaccine demonstrated promising antigenicity and immunogenicity profiles, with a favorable physical-chemical property analysis. The vaccine’s structures, designed by computational analysis, suggests high likelihood to native protein configurations. Antigenicity and allergenicity assessments validate the vaccine’s immunogenic potential and hypoallergenic nature. Physicochemical evaluations indicate favorable stability and solubility profiles, essential for vaccine efficacy. This comprehensive approach to vaccine design expressed in Chlorella vulgaris holds promises for effective salmonellosis control. The multi-epitope vaccine, designed through meticulous in-silico methods, emerges as a promising candidate for controlling salmonellosis. Its strategic construction based on the fimH protein epitopes offers a targeted approach to elicit a robust immune response, potentially curbing the spread of this disease in poultry.

Chemical composition and nutrient profiles of nine red macroalgae species

Nine red macroalgae (Amphiroa rigida, Gracilaria bursa-pastoris, Gracilaria gracilis, Grateloupia torture, Jania rubens, Laurencia obtusa, Laurencia pyramidalis, Liagora viscida, and Pterocladiella capillaries) were collected from coastal waters of Türkiye, and their proximate, fatty acid, soluble carbohydrate, and mineral profiles were investigated in the present study. According to the results, the crude protein content of the samples was between 4% and 23.8%, and four of the samples (G. turuturu, L. obtusa, L. pyramidalis, and P. capillacea) contained more than 10% protein. The crude lipid content of all the samples was below 1.6%, and the total carbohydrate content was between 38.3% and 76.9%. The macroalgae samples were generally richer in saturated fatty acids, palmitic acid being the most abundant, whereas G. gracilis had the highest content of unsaturated fatty acids (55.8%). All samples exhibited high contents of myo-inositol or glucose. Also, the samples generally had a good composition of minerals. Still, the heavy metal (i.e., Pb and Cd) content of Gracilaria gracilis was higher (59.6 µg/kg, P < 0.05) than those of the other algae samples. This study provides valuable insight into the chemical composition and fatty acid, mineral, and soluble carbohydrate profiles of Amphiroa rigida, Gracilaria bursa-pastoris, Gracilaria gracilis, Grateloupia turuturu, Jania rubens, Laurencia obtusa, Laurencia pyramidalis, Liagora viscida, and Pterocladiella capillacea from Türkiye.Graphical

Binary and Ternary Inclusion Complexes of Niflumic Acid: Synthesis, Characterization, and Dissolution Profile.

Although niflumic acid (NA) is one of the most used non-steroidal anti-inflammatory drugs, it suffers from poor solubility, low bioavailability, and significant adverse effects. To address these limitations, the complexation of NA with cyclodextrins (CDs) is a promising strategy. However, complexing CDs with low molecular weight drugs like NA can lead to low CE. This study explores the development of inclusion complexes of NA with 2-hydroxypropyl-β-cyclodextrin (2HP-β-CD), including the effect of converting NA to its sodium salt (NAs) and adding hydroxypropyl methylcellulose (HPMC) on complex formation. Inclusion complexes were prepared using co-evaporation solvent and freeze-drying methods, and their CE and Ks were determined through a phase solubility study. The complexes were characterized using physicochemical analyses, including FT-IR, DSC, SEM, XRD, DLS, UV-Vis, 1H-NMR, and 1H-ROESY. The dissolution profiles of the complexes were also evaluated. The analyses confirmed complex formation for all systems, demonstrating drug-cyclodextrin interactions, amorphous drug states, morphological changes, and improved solubility and dissolution profiles. The NAs-2HP-β-CD-HPMC complex exhibited the highest CE and Ks values, a 1:1 host-guest molar ratio, and the best dissolution profile. The results indicate that the NAs-2HP-β-CD-HPMC complex has potential for delivering NA, which might enhance its therapeutic effectiveness and minimize side effects.

ATM kinase phosphorylates Ser15 of p53 in a pH-dependent manner

The phosphorylation of Ser15 in the transactivation domain (TAD) of the tumor suppressor protein 53 (p53) by ataxia-telangiectasia mutated (ATM) kinase is a crucial step in the tumor suppressor function of p53. An understanding of the factors that affect the rate of Ser15 phosphorylation may provide new strategies for the manipulation of the ATM-p53 pathway in cancer therapy. In this study, the effect of electrostatic interactions between ATM and p53 was investigated by measuring the phosphorylation of Ser15 at varying pH ranges from 5 to 9. To achieve this, two different kinase assay methods were utilized: the ELISA technique, which directly quantifies the phosphorylated Ser15, and the Universal Kinase Assay, which assesses the formation of ADP. The results revealed that Ser15 phosphorylation was pH-dependent, with higher phosphorylation rates observed in the alkaline range. To ascertain whether the lower phosphorylation rates observed at acidic pH were due to protein denaturation, a pH-dependent solubility profile was generated using the CamSol server. The obtained results demonstrated comparable solubility rates within the pH range of the kinase assays performed. Furthermore, the significance of negatively charged residues in TAD1-39 was evaluated by substituting Asp and Glu residues with hydrophobic and uncharged hydrophilic residues in TAD1-39 using ChimeraX and subsequently comparing their interactions with the ATM using the protein-protein docking server HADDOCK2.4. The results of the docking simulations indicated that the alteration of negatively charged residues with uncharged ones resulted in a reduction in the efficiency of the interaction between the ATM and TAD1-39. In conclusion, it can be stated that electrostatic interactions between the ATM and TAD are important for optimal Ser15 phosphorylation.

Liposomal Drug Delivery: Progress, Clinical Outlook, and Ongoing Challenges

: The liposomal drug delivery system is considered an advanced drug delivery technology for formulating lipid core nano-structured particles using lipids from natural and synthetic sources. Liposomes play a wide role in improving drugs with less solubility and greater toxicity profile. Liposomes have numerous advantages, such as enhanced drug loading, good biocompatibility, prolonged drug release profile, and better pharmacokinetic properties. Numerous attempts have been made in this field in the last few years, and lots of liposomal formulations are currently being sold all over the world, and few are under clinical study. Liposomal delivery technology improves the challenges of encapsulating poor soluble drugs and maintains the stability of the formulation, along with improving the challenges of in-vivo outcomes of liposomes. The present review discussed the brief outline of the liposome drug delivery system, the innovations in the clinical application, and the significant challenges in liposomal technology.