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    Design and in vitro evaluation of curcumin-loaded PLGA nanoparticle-embedded sodium alginate/gelatin 3D printed scaffolds for Alzheimer's disease
    (Elsevier, 2024) Yekeler, Humeyra Betul; Guler, Ece; Beato, Patricia Santos; Priya, Sushma; Abobakr, Fatima Khaled Mohammed; Dogan, Murat; Uner, Burcu
    Background: Targeted nanoparticles (NPs) are aimed at improving clinical outcomes by enhancing the diagnostic and therapeutic efficacy of drugs in the treatment of Alzheimer's disease (AD). Methods: Curcumin (CUR)-loaded poly-lactic-co-glycolic acid (PLGA) NPs (CNPs) were produced to demonstrate a prolonged release and successfully embedded into 3D printed sodium alginate (SA)/gelatin (GEL) scaffolds that can dissolve rapidly sublingually. Characterization and in vitro activity of the NPs and scaffolds were evaluated. Results: Based on the in vitro drug release studies, 99.6 % of the encapsulated CUR was released in a controlled manner within 18 days for the CNPs. In vitro cell culture studies showed that all samples exhibited cell viability above 84.2 % and no significant cytotoxic effect on SH-SY5Y cells. The samples were analyzed through 2 different pathways by PCR analysis. Real-time PCR results indicated that CNP and CNP-embedded SA/GEL scaffolds (CNPSGS) may show neuroprotective effects by modulating the Wnt/beta-catenin pathway. The gene expression level of beta-catenin slightly increased compared to the gene expression levels of other proteins and enzymes with these treatments. However, the PI3K/Akt/GSK-3 beta signaling pathway was regulated at the same time because of the crosstalk between these 2 pathways. Conclusion: CNPSGS might be an effective therapeutic alternative for AD treatment.
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    In Vitro Neuroprotective Effect Evaluation of Donepezil-Loaded PLGA Nanoparticles-Embedded PVA/PEG Nanofibers on SH-SY5Y Cells and AP-APP Plasmid Related Alzheimer Cell Line Model
    (Wiley-V C H Verlag Gmbh, 2025) Guler, Ece; Yekeler, Humeyra Betul; Uner, Burcu; Dogan, Murat; Asghar, Asima; Ikram, Fakhera; Yazir, Yusufhan
    Recently developed nanoparticles and nanofibers present new brain-specific treatment strategies, especially for Alzheimer's disease treatment. In this study, donepezil (DO)-loaded PLGA nanoparticles (DNP) are embedded in PVA/PEG nanofibers (DNPF) produced by pressurized gyration for sublingual administration. SEM images showed produced drug-loaded and pure nanofibers, which have sizes between 978 and 1123 nm, demonstrated beadless morphology and homogeneous distribution. FT-IR, XRD, and DSC results proved the produced nanoparticles and fibers to consist of the DO and other polymers. The in vitro drug release test presented that the release profile of DO is completed at the end of the 18th day. It is released by the first order kinetic model. DNPF has an ultra-fast release profile via its disintegration within 2 sec, which proved itself to be suitable for the administration sublingually. All samples presented above approximate to 90% cell viability via their non-toxic natures on SH-SY5Y human neuroblastoma cells by using Alamar blue assay. The anti-Alzheimer effects of DO, DNP, and DNPF are evaluated on the A beta(1-42)-induced SH-SY5Y cells at 1, 5, and 10 mu M as treatment groups. The 1 mu M dosage exhibited the most significant neuroprotective effects, which showed enhanced cellular uptake and superior modulation of Alzheimer's-related proteins, including tau and A beta.