Browsing by Subject "Drug delivery system"
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Item Open Access The antiproliferative effect of celecoxib loaded pNIPAM nanoparticles(2012) Bayyurt, B.; Hasirci V.The aim of this study was to design a drug delivery system based on poly(N-isopropylacrylamide) (pNIPAM) nanoparticles (NPs). The model drug, Celecoxib, is a cyclooxygenase-2 inhibitor and has a great potential in chemoprevention and treatment of various cancer types, however, the clinical use is limited due to the side effects on the cardiovascular system which is most probably due to the high doses used in clinical applications. In this study, a novel nanoparticle preparation approach, nanoprecipitation, was used. The amount of crosslinker affected the size, encapsulation efficiency, loading and release rate of NPs. The antiproliferative effect of Celecoxib was tested on human osteosarcoma cells, Saos-2, and the nanoparticles were found to have cytotoxicity. Celecoxib loaded pNIPAM NPs had higher cytotoxicity and the cells treated with this formulation showed abnormal nuclear and cytoskeletal morphology indicating apoptosis. The nanoparticles were detected within the cytoplasm and their distribution differed depending on whether NP is loaded with Celecoxib or not. The drug delivery system developed in this study appears to have a potential as an antiproliferative tool in various applications such as prevention of restenosis or biofilm formation on biomaterials. © 2012 American Scientific Publishers. All rights reserved.Item Open Access Biosystems engineering of prokaryotes with tumor-killing capacities(Bentham Science Publishers Ltd., 2016) Kalyoncu, E.; Olmez, T. T.; Ozkan, A. D.; Sarioglu, O. F.Certain bacteria selectively attack tumor tissues and trigger tumor shrinkage by producing toxins and modulating the local immune system, but their clinical utility is limited because of the dangers posed by systemic infection. Genetic engineering can be used to minimize the risks associated with tumor-targeting pathogens, as well as to increase their efficiency in killing tumor cells. Advances in genetic circuit design have led to the development of bacterial strains with enhanced tumor-targeting capacities and the ability to secrete therapeutics, cytotoxic proteins and prodrug-cleaving enzymes, which allows their safe and effective use for cancer treatment. The present review details the recent advances in the design and application of these modified bacterial strains.Item Open Access Drug delivery system based on cyclodextrin-naproxen inclusion complex incorporated in electrospun polycaprolactone nanofibers(Elsevier, 2014) Canbolat, M. F.; Celebioglu A.; Uyar, TamerIn this study, we select naproxen (NAP) as a reference drug and electrospun poly (e-caprolactone) (PCL) nanofibers as a fibrous matrix for our drug-delivery system. NAP was complexed with beta-cyclodextrin (βCD) to form inclusion complex (NAP-βCD-IC) and then NAP-βCD-IC was incorporated into PCL nanofibers via electrospinning. The incorporation of NAP without CD-IC into electrospun PCL was also carried out for a comparative study. Our aim is to analyze the release profiles of NAP from PCL/NAP and PCL/NAP-βCD-IC nanofibers and we investigate the effect of CD-IC on the release behavior of NAP from the nanofibrous PCL matrix. The characterization of NAP-βCD-IC and the presence of CD-IC in PCL/NAP-βCD-IC nanofibers were studied by FTIR, XRD, TGA, NMR and SEM. The SEM imaging of the electrospun PCL/NAP and PCL/NAP-βCD-IC nanofibers reveal that the average fiber diameter of these nanofibers is around 300. nm, in addition, the aggregates of CD-IC in PCL/NAP-βCD-IC nanofibers is observed. The release study of NAP in buffer solution elucidate that the PCL/NAP-βCD-IC nanofibers have higher release amount of NAP than the PCL/NAP nanofibers due to the solubility enhancement of NAP by CD-IC.Item Open Access Evidence-Based Clinical Use of Nanoscale Extracellular Vesicles in Nanomedicine(American Chemical Society, 2016-03) Fais, S.; O'Driscoll, L.; Borras, F. E.; Buzas, E.; Camussi, G.; Cappello, F.; Carvalho, J.; Cordeiro Da Silva, A.; Del Portillo, H.; El Andaloussi, S.; Ficko Trček, T.; Furlan, R.; Hendrix, A.; Gursel, I.; Kralj-Iglic, V.; Kaeffer, B.; Kosanovic, M.; Lekka, M. E.; Lipps, G.; Logozzi, M.; Marcilla, A.; Sammar, M.; Llorente, A.; Nazarenko, I.; Oliveira, C.; Pocsfalvi, G.; Rajendran, L.; Raposo, G.; Rohde, E.; Siljander, P.; Van, N. G.; Vasconcelos, M. H.; Yáñez-Mó, M.; Yliperttula, M. L.; Zarovni, N.; Zavec, A. B.; Giebel, B.Recent research has demonstrated that all body fluids assessed contain substantial amounts of vesicles that range in size from 30 to 1000 nm and that are surrounded by phospholipid membranes containing different membrane microdomains such as lipid rafts and caveolae. The most prominent representatives of these so-called extracellular vesicles (EVs) are nanosized exosomes (70-150 nm), which are derivatives of the endosomal system, and microvesicles (100-1000 nm), which are produced by outward budding of the plasma membrane. Nanosized EVs are released by almost all cell types and mediate targeted intercellular communication under physiological and pathophysiological conditions. Containing cell-type-specific signatures, EVs have been proposed as biomarkers in a variety of diseases. Furthermore, according to their physical functions, EVs of selected cell types have been used as therapeutic agents in immune therapy, vaccination trials, regenerative medicine, and drug delivery. Undoubtedly, the rapidly emerging field of basic and applied EV research will significantly influence the biomedicinal landscape in the future. In this Perspective, we, a network of European scientists from clinical, academic, and industry settings collaborating through the H2020 European Cooperation in Science and Technology (COST) program European Network on Microvesicles and Exosomes in Health and Disease (ME-HAD), demonstrate the high potential of nanosized EVs for both diagnostic and therapeutic (i.e., theranostic) areas of nanomedicine.Item Open Access Gemcitabine integrated nano-prodrug carrier system(American Chemical Society, 2017) Hamsici, S.; Ekiz, M. S.; Ciftci, G. C.; Tekinay, A. B.; Güler, Mustafa O.Peptide nanomaterials have received a great deal of interest in drug-delivery applications due to their biodegradability, biocompatibility, suitability for large-scale synthesis, high drug-loading capacities, targeting ability, and ordered structural organization. The covalent conjugation of drugs to peptide backbones results in prolonged circulation time and improved stability of drugs. Therapeutic efficacy of gemcitabine, which is used for breast cancer treatment, is severely compromised due to its rapid plasma degradation. Its hydrophilic nature poses a challenge for both its efficient encapsulation into nanocarrier systems and its sustained release property. Here, we designed a new peptide prodrug molecule for the anticancer drug gemcitabine, which was covalently conjugated to the C-terminal of 9-fluorenylmethoxy carbonyl (Fmoc)-protected glycine. The prodrug was further integrated into peptide nanocarrier system through noncovalent interactions. A pair of oppositely charged amyloid-inspired peptides (Fmoc-AIPs) were exploited as components of the drug-carrier system and self-assembled into one-dimensional nanofibers at physiological conditions. The gemcitabine integrated nanoprodrug carrier system exhibited slow release and reduced the cellular viability of 4T1 breast cancer cell line in a time- and concentration-dependent manner.Item Open Access Injectable in situ forming microparticles: A novel drug delivery system(2012) Yapar, E. A.; Inal, Ö.; Özkan, Y.; Baykara, T.Pharmaceutical formulation research has recently been focusing on delivery systems which provide long therapeutic effects and reduced side effects, and involving simplified production stages and facilitated application process. In situ forming microparticle (ISM) systems, one of the latest approach in this field, offer a new encapsulation technique and meet the objectives stated above. Factors such as the carrier used to form the multiparticles, amount and type of drug and the vehicle type can be taken as the main performance criteria for these systems. Ongoing studies have shown that this new multiparticulate drug delivery system is suitable for achieving new implant delivery system with low risk of dose-dumping, capable of being modulated to exhibit varying release patterns, reproducible, easily applicable and welltolerated compared with classically surgical implants.Item Open Access Local delivery of doxorubicin through supramolecular peptide amphiphile nanofiber gels(Royal Society of Chemistry, 2017) Cinar, G.; Ozdemir, A.; Hamsici, S.; Gunay, G.; Dana, A.; Tekinay, A. B.; Güler, Mustafa O.Peptide amphiphiles (PAs) self-assemble into supramolecular nanofiber gels that provide a suitable environment for encapsulation of both hydrophobic and hydrophilic molecules. The PA gels have significant advantages for controlled delivery applications due to their high capacity to retain water, biocompatibility, and biodegradability. In this study, we demonstrate injectable supramolecular PA nanofiber gels for drug delivery applications. Doxorubicin (Dox), as a widely used chemotherapeutic drug for breast cancer treatment, was encapsulated within the PA gels prepared at different concentrations. Physical and chemical properties of the gels were characterized, and slow release of the Dox molecules through the supramolecular PA nanofiber gels was studied. In addition, the diffusion constants of the drug molecules within the PA nanofiber gels were estimated using fluorescence recovery after the photobleaching (FRAP) method. The PA nanofiber gels did not show any cytotoxicity and the encapsulation strategy enhanced the activity of drug molecules on cellular viability through prolonged release compared to direct administration under in vitro conditions. Moreover, the local in vivo injection of the Dox encapsulated PA nanofiber gels (Dox/PA) to the tumor site demonstrated the lowest tumor growth rate compared to the direct Dox injection and increased the apoptotic cells within the tumor tissue for local drug release through the PA nanofiber gels under in vivo conditions.Item Open Access Microfluidic device for synthesis of chitosan nanoparticles(ASME, 2013) Çetin, Barbaros; Taze, Serdar; Asik, M.D.; Tuncel, S.A.Chitosan nanoparticles have a biodegradable, biocompatible, non-toxic structure, and commonly used for drug delivery systems. In this paper, simulation of a microfluidic device for the synthesis of chitosan nanoparticle is presented. The flow filed together with the concentration field within the microchannel network is simulated using COMSOL Multiphysics® simulation environment. Different microchannel geometries are analyzed, and the mixing performance of these configurations are compared. As a result, a 3D design for a microfluidics platform which includes four channel each of which performs the synthesis in parallel is proposed. Future research directions regarding the fabrication of the microfluidic device and experimentation phase are addressed and discussed. Copyright © 2013 by ASME.Item Open Access Non-covalent functionalized SWNTs as delivery agents for novel Bodipy-based potential PDT sensitizers(2009) Erbas, S.; Gorgulu, A.; Kocakusakogullari, M.; Akkaya, E. U.Pyrenyl-functionalized distyryl-Bodipy sensitizer attached non-covalently to SWNTs was shown to generate singlet oxygen when excited at 660 nm with a red LED array; this work emphasizes the potential of SWNT as a viable alternative carrier of bioactive agents, including photodynamic therapy sensitizers. © 2009 The Royal Society of Chemistry.