The present study aimed to develop and statistically optimize immediate-release tablets of dapagliflozin using Response Surface Methodology (RSM) to achieve rapid drug release with acceptable tablet quality attributes. Immediate-release tablets of dapagliflozin were prepared by direct compression using varying concentrations of crosspovidone and starch. A three-level factorial design (32) was employed to optimize the formulation, where crosspovidone (X1) and starch (X2) served as independent variables, while hardness (Y1), disintegration time (Y2), and time required for 100
This review measured how often, and in what context, the U.S. Food and Drug Administration (FDA) refers to artificial intelligence (AI), including generative AI, in warning letters. A search was conducted of the full text of all FDA warning letters issued from January 1, 2022, through September 28, 2026, taken from FDA’s public warning letter database. The search terms were “artificial intelligence,” “AI,” “machine learning,” and 4 related terms. Every letter containing a term was assessed and read in full, and the violations cited in each included letter were counted. Form FDA 483s and establishment inspection reports (EIRs) that refer to AI were described separately. Of 3,011 warning letters, 7 (0.23
Cardiac hypertrophy is a key contributor to adverse remodeling and the progression of cardiovascular diseases. Ponatinib, a multi-targeted tyrosine kinase inhibitor approved for oncology, has been shown to inhibit growth factor signaling pathways implicated in hypertrophy. This study aimed to investigate the molecular targets of Ponatinib and evaluate its effects on cardiac hypertrophy. Network pharmacology was used to identify Ponatinib-associated targets and their overlap with cardiac disease-related genes. Protein–protein interaction (PPI) analysis, Gene Ontology (GO) analysis, and KEGG pathway enrichment analysis were performed to identify key pathways. Molecular docking assessed binding affinities with selected targets. In vitro validation was conducted in H9C2 (2–1) cells subjected to high-salt-induced hypertrophy, in which cell viability, cell size, and α-smooth muscle actin (α-SMA) levels were measured. Twenty-four overlapping targets were identified, with EGFR, MAPK8, MAP3K7, JAK2, and PDGFRB as key regulators enriched in MAPK and PI3K-Akt pathways. Docking showed strong binding affinities, particularly with PDGFRB and JAK2. In vitro, Ponatinib (0.25 µM) significantly reduced cardiomyocyte hypertrophy while maintaining cell viability. However, no significant reduction in α-SMA levels was observed. Ponatinib attenuates cardiac hypertrophy through multi-target modulation of growth factor signaling pathways. Further studies are needed to explore its role in cardiac hypertrophy.
Chronic wounds represent a major clinical challenge due to persistent inflammation, infection, and impaired tissue regeneration. This narrative review aims to critically evaluate recent advances in multifunctional biomaterial-based therapeutic strategies, with a focus on tri-modal systems combining exosomes, hydrogel scaffolds, and silver nanoparticles for enhanced wound healing. Relevant literature was identified through structured searches of PubMed, Scopus, and Web of Science up to January 2026 using combinations of the terms “exosomes,” “extracellular vesicles,” “hydrogel,” “silver nanoparticles,” “AgNPs,” “wound healing,” “nanocomposites,” and “biomaterials.” Primary studies were prioritized, particularly recent and mechanistically informative reports, while selected review articles and landmark publications were included to provide context. Studies not directly related to wound healing or lacking relevance to the tri-modal therapeutic framework were excluded from the core synthesis. Recent advances demonstrate that exosomes, hydrogels, and silver nanoparticles each contribute distinct therapeutic benefits to wound healing. Exosomes provide bioactive signaling molecules that regulate inflammation, angiogenesis, and tissue regeneration. Hydrogels serve as three-dimensional matrices enabling sustained, localized delivery of therapeutic agents. Silver nanoparticles offer potent antimicrobial activity. Their integration into tri-modal platforms enables complementary modulation of the wound microenvironment, effective infection control, and enhanced tissue repair. Key mechanistic interactions, material design considerations, and therapeutic outcomes from recent studies are critically discussed. However, challenges related to scalability, reproducibility, safety, and clinical translation remain significant. Importantly, the evidence discussed in this review is derived predominantly from preclinical in vitro and in vivo studies, and clinical efficacy and safety remain to be established. Tri-modal biomaterial systems represent a promising and conceptually advanced approach in regenerative medicine for chronic wound management. Although not yet clinically approved, these integrated platforms have substantial potential to improve therapeutic outcomes, contingent upon overcoming current translational and regulatory challenges.
This study evaluated the antidiabetic and cytotoxic effects of oleanolic acid (OA)- and asiatic acid (AA)-loaded solid lipid nanoparticles (SLNs) compared to their free compounds. The α-amylase inhibitory assay was conducted using a standard protocol, and glucose quantification in HepG2 cells was evaluated using an Accu-Chek Active glucose meter under intermittent and non-fasting conditions. Cytotoxicity was assessed on HepG2, HEK293, and Caco-2 cell lines using the MTT assay. OA and AA were docked at the active sites of an α-amylase receptor, 3BAJ, and an α-glucosidase receptor, 5NN8. The proteins were prepared using the Protein Preparation Wizard and LigPrep modules in the Schrödinger suite, employing the OPLS4 force field. Docking was performed using standard precision (SP) and extra precision (XP) methods, and the binding free energy was calculated using the MMGBSA method. The complexes of OA, AA, acarbose, and the unbound (APO) protein were solvated using the system builder package on the Schrodinger suite. Both OA- and AA-loaded SLNs and their free compounds showed α-amylase inhibitory properties with no significant difference (P > 0.05) between the SLN formulations and their free compounds. The IC50 values were 39.41 µM for OA, 42.26 µM for OA-loaded SLNs, and 17.81 µM for acarbose. In contrast, the IC50 values were 143.85 for AA, 112.75 for AA-loaded SLNs, and 30.21 µM for acarbose. Treatments with HGMet, OA25, OA-SLNs25, OA50, OA-SLNs50, and AA-SLNs50 reduced glucose concentrations in the treatment medium (P < 0.05). Similarly, glucose levels were significantly reduced in the culture medium with HGMet-IF, OA-IF25, OA-SLNs-IF25, AA-IF25, OA-IF50, OA-SLNs-IF50, AA-IF50, and AA-SLNs-IF50 treatments (P < 0.05). OA- and AA-loaded SLNs and their free compounds showed little or no toxicity in HepG2, HEK293, and Caco-2 cell lines. Molecular docking scores of OA showed weaker binding affinity to α-amylase and α-glucosidase than AA, with acarbose having the strongest binding affinity. All protein-ligand complexes were stable, as indicated by RMSD values below 2.0 Å and relatively low RMSF values. OA- and AA-loaded SLNs and their free compounds showed α-amylase inhibitory potential and reduced glucose concentration in the treatment medium, suggesting improved glucose uptake with low cytotoxicity. These results support the antidiabetic properties of SLNs loaded with OA and AA and highlight the need to further evaluate their efficacy and safety.
