LEE- Tekstil Mühendisliği Lisansüstü Programı
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ÖgeComposite nanofiber patches for topical drug delivery systems(Graduate School, 2021-04-19) Barbak, Zarife ; Karakaş, Hale ; 503122805 ; Textile Engineering ; Tekstil MühendisliğiNanofibers are ultrafine, continuous, solid state textile fibers that have diameters less than 1 micrometre. Nanofibers possess remarkable properties such as high interconnected porosity, specific surface area, ability to imitate the Extra Cellular Matrix (ECM) and potential carrier for drug delivery. Due to these fascinating properties, nanofibers are attractive candidates for medical applications for instance wound dressings, tissue scaffolds and artificial blood vessels. Electrospinning is the simplest and most practical among all methods to produce fine fibers with diameters ranging from micrometres to nanometres. Basic electrospinning equipment includes a high voltage source, a solution feeding unit, a syringe with a tip and a collector. At first, high voltage is applied to the polymer solution to produce an electrical field between the tip and the collector to shape the droplet on the tip as Taylor Cone. When the electrostatic force is higher than the surface tension of the polymer solution, polymer jet is ejected from the tip to the collector. Then, polymer jet reaches to collector following a spiral way by getting longer and thinner. Finally, nanoscale fibers are obtained on the collector. Topical drug delivery systems are composed of a formulation that applied to the skin directly to heal disorders or disease of the skin which guide/target pharmacological effect of the drug to the skin surface. Different pharmaceutical dosage forms can be used in topical drug delivery such as gels, creams, ointment, liquid preparation, sprays and solid powders. Electrospun nanofibers are excellent materials for drug delivery systems due to high interconnected porosity, high surface area, ability to imitate the Extra Cellular Matrix (ECM), potential carrier for drug delivery. Utilization of nanofibers in drug delivery systems is based on the principle that the high surface area of the nanofibrous formulation increases the dissolution rate of the drug. Compared with other dosage forms such as; liposomes, micelles and hydrogels, major advantages of nanofibers are increment in drug loading efficiency and loading capacity, low systemic toxicity and excellent stability. Furthermore, several drugs can be carried within nanofibers with high local drug concentration due to their excellent targeting and drug transportation ability in a safe way. Electrospinning offers the opportunity for direct loading of drugs or biological agents for instance antibacterial molecules, antibiotics, enzymes, growth factors, proteins, peptides, vitamins, DNA into the electrospun nanofibers. Poly (ε-caprolactone) (PCL), Poly Lactic Acid (PLA) and Poly (ethylene oxide) (PEO) were used as carrier polymers for drug delivery. PEO is a highly aqueous soluble polymer, that interacts with the body fluid quickly due to its hydrophilicity resulting in dissolution. PEO is widely used in the polymer matrix to enhance bioavailability and solubility of drugs because of its high aqueous solubility and unique properties in drug delivery applications. The compatibility of PCL and PLA with different types of drugs enables uniform drug distribution in the polymer matrix and the slow degradation rate makes them favourable for prolonged drug delivery systems. In recent years, various studies were reported on the fabrication of drug delivery systems, generated by electrospinning of PCL, PEO, PLA and their blends. PCL, PEO, PLA nanofibers or their blends were loaded with different drugs and biological agents such as; Niclosamide, Silver nanoparticles, Vitamin B12, Curcumin, Lysozyme, AgNO3, Metronidazole (MNA). Polymer blending is an effective approach to prepare functional nanofibers by incorporating the favourable properties of the component polymers. Furthermore, polymer blending facilitates the manipulation of physical, mechanical or biochemical properties of nanofibers. Hydrophilic/hydrophobic polymer blends have been electrospun into nanofibers to fabricate controlled DDS. The hydrophobic polymer forms the backbone structure and it degrades slowly, creating a long term but steady-state drug release. On the other hand, the hydrophilic polymer degrades with a more rapid process, faster than hydrophobic, which accelerates the drug release. In this study, hydrophilic water-soluble PEO was selected for the polymer matrix to enhance the solubility and bioavailability of insoluble SSD. The hydrophobic character of PCL and PLA offers a long period SSD release therefore hydrophilic PEO was blended with hydrophobic PCL and PLA. Thus, PCL/ PEO and PLA/PEO composite polymer matrix was used to provide both increased solubility and controlled release of SSD. Silver sulfadiazine (SSD) is a non-ionized, water-insoluble, topical agent with a wide range of antimicrobial activity that is affected both on bacteria and fungi. SSD is a sulfonamide based drug that is formed by the reaction of sulfadiazine with silver nitrate to form complex silver salt. SSD is used extensively in the topical treatment of infected burns. Silver sulfadiazine provides a long-term release of silver ions, whereas in the case of other silver salts, such as silver nitrate, large amounts of silver ions are released all at once. Thus, the use of SSD decreases the need for frequent application. This makes SSD a desirable and favourable agent since the frequent application is not always practical or possible for patients. However, the low aqueous solubility (3.4 mg/l at pH = 6.8) restricts the drug efficiency, bioavailability and potential antimicrobial activity of SSD thus its applications are limited. Drug solubility is an important issue since efficient drug release and antimicrobial efficiency is contributed just by decomposition of SSD to sulfadiazine and silver ions. Also, the solubility problem of SSD makes it difficult to be stabilized and incorporated into the polymer matrix. The aim of the thesis is to produce a novel SSD loaded topical drug delivery system by using advantages of electrospun nanofibers. Also, a new buffer, Water/Propylene Glycol/ Phosphoric Acid (82:16:2) was utilized to investigate the dissolution and release behaviour of SSD. Thereby SSD containing PCL/PEO and PLA/PEO composite nanofiber carriers were electrospun to achieve the enhancement in solubility, effective drug release and efficient drug loading of SSD. For this purpose, initially, the water-insoluble SSD was incorporated into highly aqueous soluble PEO to increase the solubility. Afterwards, the PEO+SSD solution was blended with PCL and PLA solution to produce composite PCL/(PEO+SSD) and PLA/(PEO+SSD) nanofibers and PCL/(PEO+SSD) casting films for topical drug delivery. SEM method was used to enable the observations of fiber defects and irregularities in the nanofibers structures and to measure the average fiber diameters of the nanofibers. The morphological characterization of the casting films was carried out by SEM and Optical Profilometer. Energy dispersive spectra (EDS) analysis was performed to confirm that the composite nanofibers and casting film which contain SSD, by detecting the Silver (Ag), Nitrogen (N), Sulphur (S) content of the nanofibers. Moreover, EDS-Mapping was carried out to show the distributions of these elements in the composite nanofibers and casting films. The stability of SSD in the fiber structure and the molecular interactions in the drug-free and drug loaded nanofibers were examined by Attenuated Total Reflectance Infrared (FTIR-ATR) Spectroscopy. The crystalline structure of the SSD loaded composite electrospun nanofibers were investigated with X-ray diffraction (XRD) analysis. Atomic Force Microscopy (AFM) was used to determine the surface roughness of the composite nanofibers. 3D AFM Images show the roughness structure of nanofibers. Water contact angle measurements were performed to evaluate the wettability properties of the fabricated nanofibers and casting films surfaces. In vitro drug release media and release conditions were optimized and the controlled drug release profile was obtained for 24 hours. Drug loading efficiency of the nanofiber formulations and casting film were calculated. To understand the SSD drug release mechanisms from SSD loaded formulations; Zero Order, First Order, Higuchi, Hixon Crowell and Korsmeyer-Peppas kinetics models were applied in the drug release profiles of the formulations. Drug release studies were also verified with conductivity measurement due to the conductive nature of SSD. Antibacterial activities of the composite nanofibers against gram-positive Staphylococcus aureus (S. aureus) and gram negative Pseudomonas Aeruginosa (P. aeruginosa) Escherichia coli (E. Coli) bacteria were performed for the period of 24, 48 and 72 hours according to disc diffusion test method. Also, the antibacterial activity of commercial SSD cream was tested for comparison with nanofiber formulations. Furthermore, antibacterial activity of the SSD loaded PCL/PEO and PLA/PEO nanofibers were examined with determining MIC and MBC values. Stability studies of the composite nanofibers were done for 3 and 6 months periods. Nanofiber samples were kept both at refrigerator conditions (+4ºC) and room conditions (25ºC ±2 and 65 % ±2ºC relative humidity) to evaluate stability of nanofiber patches. Stability tests were performed with calculating drug loading amount, cumulative drug release by UV absorption measurements and analysing surface morphology by SEM analysis. Finally, the cytotoxicity studies of the drug loaded and drug-free PCL/PEO and PLA/PEO nanofiber patches were done with using the cell viability assay (MTT assay).
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ÖgeDevelopment of textile based temperature sensor for wearable electronics(Graduate School, 2021-09-30) Arman Kuzubaşoğlu, Burcu ; Kurşun Bahadır, Senem ; 503122802 ; Textile EngineeringDue to their compressibility, bendability, and compatibility with irregular and curvilinear surfaces, flexible and stretchable devices are attracting attention and have a wide range of applications. The increasing number of publications in this field demonstrates the growing popularity of flexible sensors. Flexible sensors provide mechanical robustness, biocompatibility, multifunctionality, and comfort when compared to conventional rigid sensors. For this reason, next-generation wearable technologies are expected to be driven by interest in flexible, stretchable, and soft devices. Textiles, in addition to their protective and aesthetic functions, provide an exceptional flexible platform for providing sensing functions and comfort to the wearer with diverse range of fibers, yarns, and fabric structures. New developments in printed electronics enable mass production of sensors using efficient printing processes by considerably minimizing costs and enhancing the potential of large-scale production. In this thesis, at first, the capabilities of temperature sensors, their sensing method, and previous research that has been conducted on them are presented. Additionally, the techniques and uses of inkjet printing are examined in detail. A comprehensive explanation of inkjet printing technology and printing challenges are issued. Dispersion is required for the development of inks that include carbon nanotubes. Due to the hydrophobic nature of carbon nanotubes, they must be distributed using a combination of mechanical and chemical methods. Numerous methods, including ultrasonication, non-covalent and covalent alterations, were used to disperse nanotubes. The use of various types of carbon nanotubes in CNT ink formulations is also studied. The development of conductive inks formulations containing CNT, PEDOT:PSS and CNT/PEDOT:PSS with a proper evaluation guideline is studied. Moreover, the concepts and properties of functional materials, as well as the critical additives used during the printing process that can have a significant influence on the printing process of conductive inks are discussed. The physical, structural, morphological, and electrical properties of the materials are investigated using various techniques (UV-Vis, FTIR, optical profilometer, SEM, AFM, optic microscope, multimeter, etc.). With relevant to print quality, the textile basis material should be dependable, maintaining a level surface and good uniformity during the printing process. In order to create conductive material sensors for temperature measurement, the inkjet printing process was used, which has the advantage of reducing ink waste while also being a low-cost and simple method. Following the procurement of CNT-based inkjet suitable dispersion, a PEDOT:PSS/CNT composite ink and a PEDOT:PSS inkjet appropriate dispersion are manufactured for temperature sensing. Appropriate ink formulations have been developed to produce high-quality inkjet-printed sensors, which are typically characterized by low imperfection points throughout the surface of the printing material. The sensor manufacturing process is then completed by including silver yarn, followed by the application of silver based conductive glue and an encapsulating operation. Spectrophotometer studies were conducted to determine the qualities of carbon nanotube printing when many print passes are used, as well as the color characteristics of the produced specimens. The properties of CNT based, PEDOT:PSS based and CNT/PEDOT:PSS composite based sensors are compared to investigate their temperature sensing performance. Hence, proper ink formulations with appropriate physical and chemical properties that typically affects homogeneous printing surface characteristics and sensing properties, were successfully developed by analysing their morphologies and printing parameters. It was determined whether the printed temperature sensors performed properly by subjecting them to a temperature range ranging from 25 to 50 degrees Celsius. Furthermore, wear and performance tests, such as durability against bending, folding, humidity, rubbing, washing, light, and human sweat, were carried out with the help of some characterization methodologies in order to investigate the sensor's reliability and durability under unfavorable situations. The sensor real time measurement using of a mannequin and human gloved hand are reported with discussions. As a result, during our proof-of-concept inquiry, our newly designed temperature sensor was placed to a mannequin's skin and human body on a gloved hand for temperature monitoring. Our developed wearable sensor provides highly accurate temperature monitoring. Lastly, the application based on artificial intelligence for the modeling of wearable sensors in various temperature and humidity conditions is described. Artificial neural networks (ANN) are used to model wearable sensors in various temperature and humidity conditions. The relationship between temperature, humidity, and electrical resistance is presented with the use of ANN. This innovative wearable temperature sensor development process is expected to aid development of smart wearable technologies. The developed sensor with its good mechanical properties and excellent sensing performance is believed to be useful for use in the textile products. Moreover, this developed sensor also offers the opportunity to be directly included in wearable smart systems in industrial production. In addition to the lack of standardized and consistent manufacturing techniques, there are unfortunately not yet any regular and comparable tests that can be used for the development and implementation of wearable e-textile sensors. Hence, this study will pave a way for development phases and implemenation of wearable e-textile sensors, in particular, contribute to industrialization in this area. To conclude, the developed textile-based sensor might be a solution instead of rigid device components for human body temperature monitoring and it can be directly utilized by sticking the sensor on various garment types while maintaining the user's comfort. Hence, it reveals a strong potential for use in wearable healthcare and biomedical applications.