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Ozturk, N.

Publications and source records attributed to Ozturk, N..

3 recordsLinked to original sources

Optimizing Niosome Formulations for Enhanced Cellular Applications: A Comparative Case Study with L-α-lecithin Liposomes

This study delves into the optimization of niosome production for biological applications, focusing on their emerging role as amphiphilic nanoparticles derived from nonionic surfactants, poised at the forefront of biomedical research. We aimed to formulate and characterize a diverse array of niosomal nanoparticles, with particular emphasis on process-related parameters and physicochemical characteristics. Critical thresholds for size, polydispersity, and zeta potential were established to identify parameters crucial for optimal niosomal formulations through a comprehensive investigation of concentrations, sonication times, ingredient ratios, and surfactant types. Leveraging MODDE(R) software, we generated ten optimized formulations from preliminary parameter screening. The proposed experimental model design by the software exhibited acceptable similarity to the obtained experimental results (F-score:0.83). The criteria for selection of the predicted experimental model formed based on targeted physicochemical considerations. To enhance half-life and penetration, especially in higher electrostatic regions like the Central Nervous System (CNS), we proposed a neutralized surface charge (-10 to 10 mV) while maintaining size within 100-200 nm and polydispersity below 0.5. Extended stability screening revealed periodic and extended Gaussian distributions for size and zeta potential to minimize flocculation and coagulation caused by neutralized surface charge. Notably, the cellular response performance of optimized niosomes was assessed via cellular binding, uptake, and viability in comparison to liposomes. Glioblastoma cell line (U-87) and granulocyte colony-stimulating factor (G-CSF) containing lymphoblastic leukemia cell line (NFS-60) were chosen to represent tumors developed in the CNS region and white blood cells, respectively, enabling a comprehensive comparative analysis with liposomes. The meticulous comparison between niosomes and liposomes revealed comparable cellular viability profiles on both U-87 and NFS-60 cell lines, highlighting their similarities in cellular interactions. Moreover, selected niosomal formulations demonstrated exceptional cellular uptake, either equaling or surpassing observed liposomal uptake. One of the most promising niosomes was selected and optimized to evaluate drug encapsulation performance of niosomes for further drug delivery adaptations by one of chemotherapy drugs, Paclitaxel (PTX). Cytotoxicity study was established with the most efficiently encapsulated niosome condition with human-derived fibroblasts (HDFs) and U-87 as the representation of healthy and cancerous cell lines. Results demonstrated 1:100 diluted PTX-loaded niosome in the certain concentration demonstrated favourable toxicity in U-87 than original PTX at the same concentration while not disturbing healthy HDFs. These findings underscore the potential of niosomes for reliable drug delivery, challenging the dominance of liposomal vehicles and presenting economically viable nanocarriers with significant implications for advancing biomedical research.

bioengineering↗

TW68, Cryptochromes stabilizer, regulates fasting blood glucose level in ob/ob and fat-induced diabetic mice

Cryptochromes (CRYs), transcriptional repressors of the circadian clock in mammals, inhibit cAMP production when glucagon activates G-protein coupled receptors. Therefore, molecules that modulate CRYs have the potential to regulate gluconeogenesis. In this study, we discovered a new molecule called TW68 that interacts with the primary pockets of mammalian CRY1/2, leading to reduced ubiquitination levels and increased stability. In cell-based circadian rhythm assays using U2OS:Bmal1-dLuc cells, TW68 extended the period length of the circadian rhythm. Additionally, TW68 decreased the transcriptional levels of two genes, Phosphoenolpyruvate carboxykinase 1 (PCK1) and Glucose-6-phosphatase (G6PC), which play crucial roles in glucose biosynthesis during glucagon-induced gluconeogenesis in HepG2 cells. Oral administration of TW68 in mice showed good tolerance, a good pharmacokinetic profile, and remarkable bioavailability. Finally, when administered to fasting ob/ob and fat-induced diabetic animals, TW68 reduced blood glucose levels by enhancing CRY stabilization and subsequently decreasing the transcriptional levels of Pck1 and G6pc. These findings collectively demonstrate the antidiabetic efficacy of TW68 in vivo, suggesting its therapeutic potential for controlling fasting glucose levels in the treatment of type 2 diabetes mellitus.

molecular biology↗

Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice

Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous level of the CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis is unknown. Here, we discovered a molecule that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The small molecule, called M47, selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and the period of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 enhanced degradation rate of the CRY1 level in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced cisplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Finally, systemic repetitive administration of M47 increased the median lifespan of p53-/- mice by ~25%. Collectively our data suggest that M47 is a very promising molecule to treat forms of cancer depending on the p53 mutation.

molecular biology↗