Jéssica Ferraz, Maria Fernanda Ortolani Pollini, Vinicius Martinho Borges Cardoso
et al.
Achieving precise drug release in the colon remains a key objective in therapies for inflammatory bowel disease (IBD). Natural polysaccharides, including high-amylose starch (HAS) and pectin, offer relevant characteristics for localized drug delivery due to their biocompatibility, biodegradability, and adaptability. In this work, high-esterified pectin (HEP) was incorporated during the retrogradation of HAS to further form cohesive films without the need for organic solvents or high temperatures. The resulting matrices showed improved mucoadhesive performance, particularly under colonic conditions, where hydrophobic ester groups in HEP enhanced tissue adherence. This feature is critical for prolonged residence time in inflamed mucosa. Variations in HEP content directly influenced matrix density, fluid interaction, and mechanical resistance, without compromising film integrity. The high degree of esterification limited pH-dependent swelling and promoted alternative release mechanisms potentially related to enzymatic degradation. Such behavior contrasts with traditional low-esterified pectin (LEP) systems, suggesting that HEP may act as a structural modifier rather than a neutral excipient. Despite its widespread use in food systems, HEP remains underexplored in pharmaceutical matrices, especially in combination with retrograded starch (RS). The physicochemical and biointerfacial properties observed here underscore their applicability for the rational design of colonic delivery systems and provide a foundation for formulation strategies tailored to chronic intestinal disorders.
Noura El-Ahmady El-Naggar, Asmaa A. El-Sawah, Mohamed F. Elmansy
et al.
Abstract Gold nanoparticles (GNPs) are highly promising in cancer therapy, wound healing, drug delivery, biosensing, and biomedical imaging. Furthermore, GNPs have anti-inflammatory, anti-angiogenic, antioxidants, anti-proliferative and anti-diabetic effects. The present study presents an eco-friendly approach for GNPs biosynthesis using the cell-free supernatant of Streptomyces albogriseolus as a reducing and stabilizing agent. The biosynthesized GNPs have a maximum absorption peak at 540 nm. The TEM images showed that GNPs ranged in size from 5.42 to 13.34 nm and had a spherical shape. GNPs have a negatively charged surface with a Zeta potential of − 24.8 mV. FTIR analysis identified several functional groups including C–H, –OH, C–N, amines and amide groups. The crystalline structure of GNPs was verified by X-ray diffraction and the well-defined and distinct diffraction rings observed by the selected area electron diffraction analysis. To optimize the biosynthesis of GNPs using the cell-free supernatant of S. albogriseolus, 30 experimental runs were conducted using central composite design (CCD). The artificial neural network (ANN) was employed to analyze, validate, and predict GNPs biosynthesis compared to CCD. The maximum experimental yield of GNPs (778.74 μg/mL) was obtained with a cell-free supernatant concentration of 70%, a HAuCl4 concentration of 800 μg/mL, an initial pH of 7, and a 96-h incubation time. The theoretically predicted yields of GNPs by CCD and ANN were 809.89 and 777.32 μg/mL, respectively, which indicates that ANN has stronger prediction potential compared to the CCD. The anticancer activity of GNPs was compared to that of doxorubicin (Dox) in vitro against the HeP-G2 human cancer cell line. The IC50 values of Dox and GNPs-based treatments were 7.26 ± 0.4 and 22.13 ± 1.3 µg/mL, respectively. Interestingly, treatments combining Dox and GNPs together showed an IC50 value of 3.52 ± 0.1 µg/mL, indicating that they targeted cancer cells more efficiently.
In this study, the mucosa of porcine small intestine was used as the raw material to optimize the optimal process for the extraction of heparin (Hep) by high hydrostatic pressure enzymatic hydrolysis by response surface test, to study the adsorption conditions of Hep purified by macroporous resin, and to explore the stability of Hep (pH, temperature, and light). The results showed that the optimal enzymatic process was alkaline protease, 3.1 h, 55 ℃, pH9.5, pressure 100 MPa, enzyme addition 9%, salt concentration 2.0%, the actual average concentration of Hep was measured to be 11.56±0.12 U/mL. The purification of Hep was carried out by using the D958 resin, with the up-sampling flow rate of 1.5 BV/h, the concentration of the eluent of 4 mol/L NaCl, and the elution flow rate of 1.5 BV/h, the purity of Hep could reach 68.75% after purification, and the electrophoretic purity achieved. In the stability study, Hep had the best stability at pH7.5, better stability at 40 ℃, and light had no effect on the stability of Hep. This study can greatly improve the extraction effect of Hep and provide theoretical and technical support for the high value processing and utilization of pig small intestine.
Motivated by recent advancements in antimuon cooling, we consider Higgs boson production at µ+µ+ colliders. The leading-order W+W− fusion process present at, e.g., µ+µ− colliders does not occur since both intial-state particles carry the same charge. Nevertheless, Higgs production is possible via a higher-order process mediated by a photon or Z boson. We find that at high energies, the associated cross secction grows as (log s)3 with the center-of-mass energy √s, as opposed to the log s growth of the leading-order process at µ+µ− colliders. Thus, the higher-order cross section with polarized beams can become about half as large as the leading-order process at µ+µ− colliders at O(10) TeV energies, despite its naive suppression. When calculating the higher-order cross section, collinear photon emissions make direct computations using event generators difficult. We therefore treat these emissions by splitting the phase-space into the sum of a non-collinear region calculable using event generators, and a collinear region approximated by a parton distribution function for the photon. Furthermore, since the same process can occur at any high-energy lepton collider, this large cross section needs to be considered also for Higgs production at µ+µ− and e+e− colliders.
Yi-Wei Chen, Muhammad Haseeb Iqbal, Florent Meyer
et al.
The surface properties of a biomaterial play an important role in cell behavior, e.g., recolonization, proliferation, and migration. Collagen is known to favor wound healing. In this study, collagen (COL)-based layer-by-layer (LbL) films were built using different macromolecules as a partner, i.e., tannic acid (TA), a natural polyphenol known to establish hydrogen bonds with protein, heparin (HEP), an anionic polysaccharide, and poly(sodium 4-styrene sulfonate) (PSS), an anionic synthetic polyelectrolyte. To cover the whole surface of the substrate with a minimal number of deposition steps, several parameters of the film buildup were optimized, such as the pH value of the solutions, the dipping time, and the salt (sodium chloride) concentration. The morphology of the films was characterized by atomic force microscopy. Built at an acidic pH, the stability of COL-based LbL films was studied when in contact with a physiological medium as well as the TA release from COL/TA films. In contrast to COL/PSS and COL/HEP LbL films, COL/TA films showed a good proliferation of human fibroblasts. These results validate the choice of TA and COL as components of LbL films for biomedical coatings.
Background: Leukaemia accounts for approximately 2.5% of all new cancer incidence and 3.1% of cancer-related mortality with a significant number of the total presenting as Acute Lymphocytic Leukemia. Acute Lymphocytic Leukemia (ALL) poses a healthcare burden in the majority of the countries of the world but is more so a case in resource-limited countries where access to comprehensive healthcare is often limited and scarcely available. This article tries to highlight the challenges in ALL treatments in one such region by presenting the facts regarding treatments employed and patient outcomes seen. Method: This was a retrospective single-institution study in a tertiary care setup examining Ph neg ALL patient data from Jan 2019 to Dec 2020. It was stratified according to various parameters ranging from presentation to mode of diagnosis as well as treatment strategies and responses achieved after induction including mortality. Conventional chemotherapy regimens for ALL treatment were used with corticosteroids, vincristine, anthracyclines, asparaginase, cytosar, and MTX being the backbone of ALL induction. Cytogenetics were not possible due to resource constraints. Results: Data showed 85 patients being managed during the mentioned time period. 65 percent were males and 68 percent were between the age 15 to 30 years. Approximately 80 percent had no co-morbid condition including diabetes, hypertension, ischemic heart disease or Hep B/C positivity. Around 60 percent were diagnosed on immunophenotyping by flowcytometry and 62 percent used HyperCVAD as the induction protocol. Patients who achieved CR were 62 percent after single induction and most were assessed after count recovery on (3-4 weeks) or after 6 weeks with the percentages being 32 and 41 respectively. Duration of admission was for 1-3 weeks for almost 70 percent of the patients and those alive at the end of induction were around 90 percent. Conclusion: In conclusion, the treatment of Acute Lymphocytic Leukemia in resource-limited countries remains a formidable task,sometimes requiring innovative and sustainable approaches. Due to limited resources, a resource stratified rather than risk-stratified treatment approach is often utilized to tailor therapy. This approach ensures that relatively better resourced patients receive more intensive treatment others are spared unnecessary toxicity. While the challenges in resource-limited settings are significant, the treatment strategies and chemotherapy protocols, if modified as per need and implemented effectively, hold promise in improving outcomes for patients with Ph negative Acute Lymphocytic Leukemia in regions which have limited resources at their disposal.
The human respiratory syncytial virus (hRSV) is a major cause of serious lower respiratory infections and poses a considerable risk to public health globally. Only a few treatments are currently used to treat RSV infections, and there is no RSV vaccination. Therefore, the need for clinically applicable, affordable, and safe RSV prevention and treatment solutions is urgent. In this study, an ion-activated in situ gelling formulation containing the broad-spectrum antiviral 18β-glycyrrhetinic acid (GA) was developed for its antiviral effect on RSV. In this context, pH, mechanical characteristics, ex vivo mucoadhesive strength, in vitro drug release pattern, sprayability, drug content, and stability were all examined. Rheological characteristics were also tested using in vitro gelation capacity and rheological synergism tests. Finally, the cytotoxic and antiviral activities of the optimized in situ gelling formulation on RSV cultured in the human laryngeal epidermoid carcinoma (HEp-2) cell line were evaluated. In conclusion, the optimized formulation prepared with a combination of 0.5% <i>w</i>/<i>w</i> gellan gum and 0.5% <i>w</i>/<i>w</i> sodium carboxymethylcellulose demonstrated good gelation capacity and sprayability (weight deviation between the first day of the experiment (T0) and the last day of the experiment (T14) was 0.34%), desired rheological synergism (mucoadhesive force (Fb): 9.53 Pa), mechanical characteristics (adhesiveness: 0.300 ± 0.05 mJ), ex vivo bioadhesion force (19.67 ± 1.90 g), drug content uniformity (RSD%: 0.494), and sustained drug release over a period of 6 h (24.56% ± 0.49). The optimized formulation demonstrated strong anti-hRSV activity (simultaneous half maximal effective concentration (EC<sub>50</sub>) = 0.05 µg/mL; selectivity index (SI) = 306; pre-infection EC<sub>50</sub> = 0.154 µg/mL; SI = 100), which was significantly higher than that of ribavirin (EC<sub>50</sub> = 4.189 µg/mL; SI = 28) used as a positive control against hRSV, according to the results of the antiviral activity test. In conclusion, this study showed that nasal in situ gelling spray can prevent viral infection and replication by directly inhibiting viral entry or modulating viral replication.
Hericium erinaceus polysaccharides (HEPs) have attracted widespread attention in regulating gut microbiota (GM). To investigate digestibility and fermentation of HEPs and their effects on GM composition, three polysaccharide fractions, namely, HEP-30, HEP-50, and HEP-70, were fractionally precipitated with 30%, 50%, and 70% ethanol concentrations (v/v) from hot water-soluble extracts of Hericium erinaceus, respectively. Three kinds of prepared HEPs were structurally characterized and simulated gastrointestinal digestion, and their effects on human fecal microbiota fermentations of male and female and short-chain fatty acid (SCFA) production in vitro were clarified. Under digestive conditions simulating saliva, stomach, and small intestine, HEPs were not significantly influenced and safely reached the distal intestine. After 24 h of in vitro fermentation, the content of SCFAs was significantly enhanced (p < 0.05), and the retention rates of total and reducing sugars and pH value were significantly decreased (p < 0.05). Thus, HEPs could be utilized by GM, especially HEP-50, and enhanced the relative abundance of SCFA-producing bacteria, e.g., Bifidobacterium, Faecalibacterium, Blautia, Butyricicoccus, and Lactobacillus. Furthermore, HEPs reduced the relative abundances of opportunistic pathogenic bacteria, e.g., Escherichia-Shigella, Klebsiella, and Enterobacter. This study suggests that gradual ethanol precipitation is available for the preparation of polysaccharides from Hericium erinaceus, and the extracted polysaccharide could be developed as functional foods with great development value.
Fiza ur Rehman, Syeda Sohaila Naz, Muhammad Junaid Dar
et al.
Neoplastic cells have co-opted inflammatory receptors and signaling molecules that potentiate inflammation. Activated inflammatory pathways lead to neo-angiogenesis, lymph-angiogenesis, immunosuppression, tumor growth, proliferation and metastasis. This cancer-sustaining inflammation is a critical target to arrest cancer growth. Multiple drug resistance, high cost, low oral bioavailability and serious side effects have rendered conventional cytotoxic chemotherapeutics less impressive. The aim of this research was to achieve cancer debulking and proliferation prevention by limiting ‘cancer-sustaining’ tumor niche inflammation through non-conventional oral approach employing anti-inflammatory agents and avoiding conventional cytotoxic agents. Synergistic anti-inflammatory agents, i.e. celecoxib as selective COX-2 inhibitor and montelukast as cysteinyl leukotriene receptor antagonist, were selected. Silver nanoparticles (AgNPs) were used as nanocarriers because of their efficient synergistic anti-neoplastic effects and excellent oral drug delivery potential. Specifically, selected drugs were co-conjugated onto AgNPs. Synthesized nanoparticles were then surface-modified with poly(vinyl alcohol) to control particle size, avoid opsonization/preferred cellular uptake and improve dispersion. Surface plasmon resonance analysis, particle size analysis, DSC, TGA, XRD, FTIR and LIBS analysis confirmed the successful conjugation of drugs and efficient polymer coating with high loading efficiency. In-vitro, the nanoparticles manifested best and sustained release in moderately acidic (pH 4.5) milieu enabling passive tumor targeting potential. In-vivo, synthesized nanoparticles exhibited efficient dose-dependent anti-inflammatory activity reducing the dose up to 25-fold. The formulation also manifested hemo-compatibility, potent anti-denaturation activity and dose-dependent in-vitro and in-vivo anti-cancer potential against MCF-7 breast cancer and Hep-G2 liver cancer cell lines in both orthotopic and subcutaneous xenograft cancer models. The anti-inflammatory nanoparticles manifested tumor specific release potential exhibiting selective cytotoxicity at cancerous milieu with slightly acidic environment and activated inflammatory pathways. The formulation displayed impressive oral bioavailability, sustained release, negligible cytotoxicity against THLE-2 normal human hepatocytes, low toxicity (high LD50) and wide therapeutic window. Results suggest promise of developed nanomaterials as hemo-compatible, potent, cheaper, less-toxic oral anti-inflammatory and non-conventional anti-cancer agents.