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    Improving physiological solubility and gene transfer efficiency of chitosan via 3-nitrobenzaldehyde and amino acid conjugation
    (Elsevier, 2025) Bal, Kevser; Kaplan, Özlem; Şentürk, Sema; Küçükertuğrul Çelik, Sibel; Demir, Kamber; Gök, Mehmet Koray
    In this study, chitosan was chemically modified with 3-nitrobenzaldehyde (3NBA) and three amino acids (arginine, cysteine, and histidine) to enhance its gene delivery performance. 3-NBA was selected for its known DNA binding properties, while the amino acids were chosen based on their functional groups, which can improve solubility, facilitate cellular uptake, and contribute to endosomal escape. The modified chitosan polymers were characterized using Fourier Transform Infrared Spectroscopy (FTIR) and Nuclear Magnetic Resonance Spectroscopy (NMR). Nanoparticles were prepared using the ionotropic gelation method, and their particle size, polydispersity index (PDI), zeta potential were analyzed by dynamic light scattering (DLS). The particle sizes ranged from 105.07 ± 3.45 to 206.15 ± 10.39 nm, with PDI values between 0.29 ± 0.01 and 0.39 ± 0.02. Zeta potentials were measured between 32.05 ± 0.49 mV and 51.95 ± 0.35 mV. The cysteine-modified chitosan (Chi-3NBACys) exhibited approximately 8.4-fold higher solubility than unmodified chitosan. In vitro studies demonstrated that the modified chitosan nanoparticles exhibited low cytotoxicity in HEK293T cells. Among the tested formulations, Chi-3NBACys showed the highest transfection efficiency, comparable to commercial agent Lipofectamine™ 2000. These findings suggest that chitosan nanoparticles modified with 3-NBA and amino acids can be safe and efficient non-viral gene delivery vectors.
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    Nicotinic acid–modified chitosan nanoparticles for enhanced resveratrol delivery and anticancer activity
    (Wiley, 2026) Şentürk, Sema; Kaplan, Özlem; Bal, Kevser; Küçükertuğrul Çelik, Sibel; Gökşen Tosun, Nazan; Gök, Mehmet Koray
    This study focused on functionalizing chitosan with nicotinic acid, the active form of vitamin B3, to obtain a new derivative (ChiNico) with enhanced solubility at physiological pH, improved proton buffering capacity, and in vitro anticancer activity, and to develop resveratrol-loaded nanoparticles (nChiNico-RES) for enhanced anticancer performance. Chitosan was modified through EDC-mediated amidation, and successful conjugation was confirmed by FTIR, 1H NMR, and GPC/SEC analyses. Nicotinic acid grafting increased molecular weight, introduced characteristic amide signals, improved solubility at physiological pH, and enhanced proton buffering capacity. Nanoparticles were prepared by ionotropic gelation and showed sizes of 100–140nm, PDI values below 0.4, and a positive surface charge of +18 to +20mV. Blank nanoparticles exhibited minimal cytotoxicity, while resveratrol-loaded formulations demonstrated significant anticancer activity in HeLa cervical cancer cells and HT-29 human colon adenocarcinoma cell line. Notably, nChiNico-RES reduced HeLa and HT-29 cell viability more effectively than free resver atrol and nanoparticles based on unmodified chitosan, indicating an additive contribution from nicotinic acid. In contrast, the cytotoxic effect on healthy BJ fibroblasts remained considerably lower, supporting the biocompatibility and selective potential of the system. Overall, nicotinic acid modification improves chitosan's carrier performance and offers a novel strategy by combin ing two natural bioactive molecules within a single nanoparticle platform.
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    Redox-responsive and mucoadhesive nanoparticles: An overlooked synergy in modern drug delivery
    (Elsevier, 2026) Küçükertuğrul Çelik, Sibel; Şentürk, Sema; Bal, Kevser; Kaplan, Özlem; Gök, Mehmet Koray
    The continuous advancement of therapeutic technologies has intensified the pursuit of drug delivery systems that respond intelligently to physiological and pathological stimuli, thereby enabling precise, localized, and sustained therapeutic outcomes. Among redox-based approaches, systems responsive to intracellular glutathione (GSH) have attracted particular attention due to their ability to trigger disulfide bond cleavage and controlled release within diseased tissues. Mucoadhesive systems, on the other hand, prolong residence time on mucosal surfaces through non-covalent interactions and covalent bond formation, thereby facilitating increased absorption and decreased clearance. Despite their individual successes, the integration of these two mechanisms remains underexplored. This review critically examines the coupling of redox sensitivity and mucoadhesion, highlighting how disulfide-based bonds can simultaneously function as both redox-cleavable and mucoadhesive moieties.