👤 Mohamed S Elnaggar

This study investigated an intranasal nose-to-brain delivery strategy to repurpose ondansetron (OND) for anxiety management using PLGA nanoparticles co-loaded with superparamagnetic iron oxide nanoparticles (SPIONs) and incorporated into a Carbopol 940 mucoadhesive gel. Nanoparticles were optimized using an I-optimal experimental design evaluating PLGA concentration and surfactant type. The optimized SPION/OND-PLGA nanoparticles showed a small particle size (141.547 ± 1.31 nm), narrow distribution (PDI = 0.235 ± 0.002), relatively high zeta potential (-34.307 ± 0.53 mV), and satisfactory encapsulation efficiency (42.09 ± 1.34%). The developed nanogel exhibited acceptable organoleptic properties, shear-thinning behavior, sustained drug release, and enhanced ex vivo nasal permeability, with OND permeation values of 996.96 ± 6.53 μg, 621.92 ± 7.54 μg, and 317.87 ± 2.88 μg per cm Show less

Crateva magna (Cm) was utilized as a folkloric medicine against neurological disorders. This study aimed to investigate the phytochemical profile of Cm leaf extract and its endophytic fungus, Nigrospora oryzae (No) extract. Additionally, the neuroprotective potential of their optimized bilosomes (BLs) will be assessed as an approach to Alzheimer's disease (AD) treatment. UPLC-ESI-MS/MS chemical profiling was performed. In vitro anti-Alzheimer activity of Cm and No extracts was evaluated against AChE and BACE1 enzymes. Cm-BLs and No-BLs were prepared using the thin-film hydration technique. In vivo anti-Alzheimer potential was assessed in a streptozotocin (STZ)-induced sporadic AD mouse model. Behavioral assays, neurochemical assays, RT-PCR analysis, histopathological examination, and immunohistochemical analysis were performed. Chemical profiling revealed diverse metabolites from various chemical classes. The major class identified in Cm extract was flavonoids, e.g., kaempferol-O-hexoside, whereas in No extract, it was alkaloids, e.g., phenazine carboxamide. The neuropathological markers (Aβ1-42, IL-6, and p-Tau protein) were reduced by ≈50% and 60% in mice receiving Cm-BLs and No-BLs, respectively, relative to the STZ group. Also, the BLs exhibited the greatest ability to downregulate the expression of p-JNK, p-P38, and p-ERK in the brain. Histopathological examination revealed that No-BLs showed the highest protection for the hippocampus and cerebral cortex regions. Also, it revealed a significantly decreased reaction for NFκB in cerebral cortex neurons. Cm-BLs and No-BLs exhibit considerable potential as novel adjuvant therapies for AD, utilizing natural bioactive compounds to improve the efficiency of targeted drug delivery and enhance therapeutic outcomes. Show less