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    A new nano approach to prevent tumor growth in the local treatment of glioblastoma: Temozolomide and rutin-loaded hybrid layered composite nanofiber
    (Shenyang Pharmaceutical Univ, 2024) Ercelik, Melis; Tekin, Cagla; Gurbuz, Melisa; Tuncbilekli, Yagmur; Dogan, Hazal Yilmaz; Mutlu, Busra; Tunca, Berrin
    Total resection of glioblastoma (GB) tumors is nearly impossible, and systemic administration of temozolomide (TMZ) is often inadequate. This study presents a hybrid layered composite nanofiber mesh (LHN) designed for localized treatment in GB tumor bed. The LHN, consisting of polyvinyl alcohol and core-shell polylactic acid layers, was loaded with TMZ and rutin. In vitro analysis revealed that LHNTMZ and LHNrutin decelerated epithelial-mesenchymal transition and growth of stem-like cells, while the combination, LHNTMZ+rutin, significantly reduced sphere size compared to untreated and LHNTMZ-treated cells (P < 0.0001). In an orthotopic C6-induced GB rat model, LHNTMZ+rutin therapy demonstrated a more pronounced tumor-reducing effect than LHNTMZ alone. Tumor volume, assessed by magnetic resonance imaging, was significantly reduced in LHNTMZ+rutin-treated rats compared to untreated controls. Structural changes in tumor mitochondria, reduced membrane potential, and decreased PARP expression indicated the activation of apoptotic pathways in tumor cells, which was further confirmed by a reduction in PHH3, indicating decreased mitotic activity of tumor cells. Additionally, the local application of LHNs in the GB model mitigated aggressive tumor features without causing local tissue inflammation or adverse systemic effects. This was evidenced by a decrease in the angiogenesis marker CD31, the absence of inflammation or necrosis in H&E staining of the cerebellum, increased production of IFN-gamma, decreased levels of interleukin-4 in splenic T cells, and lower serum AST levels. Our findings collectively indicate that LHNTMZ+rutin is a promising biocompatible model for the local treatment of GB. (c) 2024 Shenyang Pharmaceutical University. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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    Co-loading of Temozolomide with Oleuropein or rutin into polylactic acid core-shell nanofiber webs inhibit glioblastoma cell by controlled release.
    (Elsevier B.V., 2023) Ercelik, Melis; Tekin, Cagla; Parın, Fatma Nur; Mutlu, Büşra; Doğan, Hazal Yılmaz; Tezcan, Gulcin; Aksoy, Secil Ak; Gurbuz, Melisa; Yıldırım, Kenan; Bekar, Ahmet; Kocaeli, Hasan; Taskapilioglu, Mevlut Ozgur; Eser, Pinar; Tunca, Berrin
    Glioblastoma (GB) has susceptibility to post-surgical recurrence. Therefore, local treatment methods are required against recurrent GB cells in the post-surgical area. In this study, we developed a nanofiber-based local therapy against GB cells using Oleuropein (OL), and rutin and their combinations with Temozolomide (TMZ). The polylactic acid (PLA) core-shell nanofiber webs were encapsulated with OL (PLA), rutin (PLA), and TMZ (PLA) by an electrospinning process. A SEM visualized the morphology and the total immersion method determined the release characteristics of PLA webs. Real-time cell tracking analysis for cell growth, dual Acridine Orange/Propidium Iodide staining for cell viability, a scratch wound healing assay for migration capacity, and a sphere formation assay for tumor spheroid aggressiveness were used. All polymeric nanofiber webs had core-shell structures with an average diameter between 133 ± 30.7-139 ± 20.5 nm. All PLA webs promoted apoptotic cell death, suppressed cell migration, and spheres growth (p < 0.0001). PLA and PLA suppressed GB cell viability with a controlled release that increased over 120 h, while PLA caused rapid cell inhibition (p < 0.0001). Collectively, our findings suggest that core-shell nano-webs could be a novel and effective therapeutic tool for the controlled release of OL and TMZ against recurrent GB cells.
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    Curcumin-Loaded Akermanite/Chitosan/Carboxymethylcellulose Patches for Skin Wound Healing: Fabrication, Characterization, and In Vitro Cytocompatibility
    (Wiley-V C H Verlag Gmbh, 2025) Mutlu, Busra; Demirci, Fatma; Ercelik, Melis; Tekin, Cagla; Tunca, Berrin; Terzioglu, Pinar; Duman, Seyma
    In this study, bioactive and biocompatible transdermal patches were fabricated through the lyophilization of a chitosan/carboxymethylcellulose/akermanite composite matrix. The influence of curcumin incorporation at 0.5%, 1%, and 2% on the physicochemical, morphological, and biological properties of the patches was systematically investigated. Scanning electron microscopy revealed an interconnected porous structure with pore sizes ranging from 29 to 57 mu m, facilitating cell infiltration and nutrient transport. Fourier transform infrared spectroscopy and energy-dispersive X-ray spectroscopy confirmed the successful integration of akermanite and curcumin, along with characteristic interactions within the polymeric network. In vitro release studies demonstrated a biphasic profile consisting of an initial burst followed by a sustained release phase, with the CCMAKCur0.5 sample achieving the highest cumulative release (94.28%). Antioxidant performance, evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method, ranged from 21.55% (CCM) to 38.96% (CCMAKCur0.5), while higher curcumin concentrations reduced activity due to increased matrix densification. Simulated body fluid immersion confirmed apatite formation, particularly in CCMAKCur0.5 and CCMAKCur2, indicating enhanced bioactivity. Cytocompatibility studies with HUVECs showed no toxic effects, and scratch assays demonstrated that CCMAKCur0.5 most effectively promoted wound closure. Overall, the findings indicate that curcumin- and akermanite-loaded lyophilized patches represent promising candidates for transdermal therapeutic applications.