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Öğe A potential non-invasive glioblastoma treatment: Nose-to-brain delivery of farnesylthiosalicylic acid incorporated hybrid nanoparticles(Elsevier B.V., 2017) Şekerdağ, Emine; Lüle, Sevda; Bozdağ Pehlivan, Sibel; Öztürk, Naile; Kara, Aslı; Kaffashi, Abbas; Vural, İmran; Işıkay, İlkay; Yavuz, Burçin; Karlı Oğuz, Hatice Kader; Söylemezoğlu, Figen; Gürsoy Özdemir, Yasemin; Mut, MelikeNew drug delivery systems are highly needed in research and clinical area to effectively treat gliomas by reaching a high antineoplastic drug concentration at the target site without damaging healthy tissues. Intranasal (IN) administration, an alternative route for non-invasive drug delivery to the brain, bypasses the blood-brainbarrier (BBB) and eliminates systemic side effects. This study evaluated the antitumor efficacy of farnesylthiosalicylic acid (FTA) loaded (lipid-cationic) lipid-PEG-PLGA hybrid nanoparticles (HNPs) after IN application in rats. FTA loaded HNPs were prepared, characterized and evaluated for cytotoxicity. Rat glioma 2 (RG2) cells were implanted unilaterally into the right striatum of female Wistar rats. 10 days later, glioma bearing rats received either no treatment, or 5 repeated doses of 500 mu M freshly prepared FTA loaded HNPs via IN or intravenous (IV) application. Pre-treatment and post-treatment tumor sizes were determined with MRI. After a treatment period of 5 days, IN applied FTA loaded HNPs achieved a significant decrease of 55.7% in tumor area, equal to IV applied FTA loaded HNPs. Herewith, we showed the potential utility of IN application of FTA loaded HNPs as a non-invasive approach in glioblastoma treatment.Öğe Development of novel self-assembled polymeric micelles from partially hydrolysed poly(2-ethyl-2-oxazoline)-co-PEI-b-PCL block copolymer as non-viral vectors for plasmid DNA in vitro transfection(Taylor and Francis Ltd., 2018) Kara, Aslı; Öztürk, Naile; Esendağlı, Güneş; Özköse, Umut Uğur; Gülyüz, Sevgi; Yılmaz, Özgür; Telci, Dilek; Bozkır, Asuman; Vural, İmranA new efficient, non-viral gene delivery cationic polymeric micellar system was developed by partial hydrolysis of poly(2-ethyl-2-oxazoline) (PEtOx) with two different hydrolysis percentages of PEtOx (30% and 60%) to reduce the disadvantages of the PEI. These self-assemble amphiphilic cationic micelles prepared from poly(2-ethyl-2-oxazoline) 30% -co-poly(ethyleneimine)-block-poly(?-caprolactone) (PEtOx 30% -co-PEI-b-PCL) (PPP30) and poly(2-ethyl-2-oxazoline) 60% -co-poly(ethyleneimine)-block-poly(?-caprolactone) (PEtOx 60% -co-PEI-b-PCL) (PPP60) block copolymers were successfully condensed with pEGFP-C3 plasmid DNA via electrostatic interactions to form micelle/DNA complexes with desirable particle sizes. All formulations showed low critical micelle concentration (CMC) values that means highly stable in serum containing medium. Polymeric micelles were also evaluated for their stability in the presence of serum and nuclease as well as cytotoxicity and transfection efficiency. All our results proved that our novel polymeric micellar system prepared by PPP60 block copolymer offer to be an efficient promising carrier for gene delivery applications. Moreover, these findings contribute to design and development of novel gene vectors with tunable and functionality features and also to reduce the cytotoxicity of PEI by partial hydrolysis of PEtOx an alternative synthesis method to produce linear PEI. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.Öğe Evaluation of antitumor activity of a non-steroidal anti-inflammatory drug, ibuprofen, by a targeted nanoparticulate system(Colegio de Farmaceuticos de la Provincia de Buenos Aires, 2017) Öztürk, Naile; Kara, Aslı; Vural, İmranIn this study we aimed to develop a new targeted nanoparticulate system to obtain site specific delivery of ibuprofen and to determine its antitumor efficiency. The potential effect of ibuprofen as an antitumor agent was investigated on breast cancer cells based on a targeted delivery system. Ibuprofen was encapsulated to poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA nanoparticles were fabricated by nanoprecipitation method and optimized in terms of certain parameters. Then, 520C9 monoclonal antibody (mAb) was chemically conjugated to carboxylic acid end group of PLGA nanoparticles (NPs) that specifically targeted human breast adenocarcinoma cell line (MCF-7). NP-mAb combined Ibuprofen encapsulated formulations were evaluated on characterization of particle size, encapsulation efficiency, drug loading capacity, and antitumor activity. The results demonstrated that optimized Ibuprofenloaded PLGA nanoparticles prepared by nanoprecipitation technique had an ideal particle size and polydispersity index. The encapsulation efficiency of optimized nanoparticles was relatively high, 92.9 ± 9.0%. Also, this system had significantly reduced the cell viability on MCF-7 cell line when compared with free ibuprofen solution at the same concentration. Above all, antibody-conjugated nanoparticles showed lower cell viability (12%) than the non-targeted system. Results indicated that ibuprofen-loaded nanoparticles had significant antitumor activity on MCF-7 cells even at relatively low concentrations. mAb conjugated drug-loaded nanoparticles were successfully fabricated and this system might be a promising approach for delivery of ibuprofen in treatment of breast cancer. © 2017, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.Öğe Formulation and In Vitro Evaluation of Telmisartan Nanoparticles Prepared by Emulsion-Solvent Evaporation Technique(2020) Öztürk, Naile; Kara, Aslı; Vural, İmranbjectives: Telmisartan (TLM) is an antihypertensive drug that has been shown to have antiproliferative effects on cancer cells. It has low solubility and suboptimal oral bioavailability. To investigate the potential anticancer effect of TLM on breast cancer cells, poly (D, L-lactide) (PLA) nanoparticles were formulated with the benefit of improving its solubility.Materials and Methods: TLM-loaded PLA nanoparticles were prepared by emulsion solvent evaporation. The effects of sonication time and polymer:drug ratio on nanoparticle size and drug encapsulation were investigated. TLM-loaded nanoparticles were tested against MCF-7 and MDA-MB-231 breast cancer cell lines for antiproliferative effects.Results: Nanoparticles with mean particle size 272 nm and 79% encapsulation efficiency were obtained. Sustained release TLM nanoparticles (40% in 24 h) decreased cell viability to 45% for MCF-7 cells at 72 h, even at the lowest TLM concentration, indicating better anticancer efficiency than TLM solution.Conclusion: TLM nanoparticles could be potential anticancer agents for breast cancer and deserve further studies.Öğe In vitro CNS models(Elsevier, 2017) Kara, Aslı; Öztürk, Naile; Vural, İmran; Gürsoy Özdemir, Yasemin; Şekerdağ, EmineEndothelial cells form a barrier between the blood and the central nervous system, namely the blood-brain barrier (BBB). Cellular components of the BBB, as well as tight junctions and paracellular barrier characterizations, are described in this chapter. Furthermore, in vitro BBB models are classified as 2D models (monoculture and coculture), 3D, dynamic, and microfluidic models and further explained in detail. The components of the neurovascular unit and their role in obtaining special BBB properties in vitro are outlined, and methods that mimic the dynamic nature of an in vivo microenvironment are discussed. Promising approaches, such as stem cells and microfluidics, for future modeling of the BBB are also mentioned throughout this chapter. As a result it has been concluded that for drug discovery and delivery studies, which target the central nervous system, in vitro BBB models are very useful. © 2017 Elsevier Inc. All rights reserved.