LEE- Tekstil Mühendisliği Lisansüstü Programı

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http://hdl.handle.net/11527/19465

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Konu "biopolymers" ile LEE- Tekstil Mühendisliği Lisansüstü Programı'a göz atma
  • Öge
    Composite nanofiber patches for topical drug delivery systems
    (Graduate School, 2021-04-19) Barbak, Zarife ; Karakaş, Hale ; 503122805 ; Textile Engineering ; Tekstil Mühendisliği
    Nanofibers 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).
  • Öge
    Design and development of pva/hydrocortisone loaded xerogel nanofibrous mat for topical drug delivery
    (Graduate School, 2023) Moussa, Hissam Ali Muhammad Ali ; Kayaoğlu Karagüzel, Burçak ; 807298 ; Textile Engineering Programme
    Textile materials have always been utilized in the medical field. The unique properties they offer, biocompatibility and versatility are the major reasons behind that. They can be found in applications ranging from a simple bandage to full on blood vessels. Nanofiber-based textile materials are textile materials known for their high surface area and interconnected porosity. Nanofiber- based textile materials can be fabricated with a variety of methods yet; the most dominant method is electrospinning. Furthermore, in the recent years there has been a rise of interest in different materials as well such as; aerogels. Aerogels are porous materials that have unique properties that make them good candidates for drug careering and releasing. Aerogels can be made of different materials such as polymers, biopolymers and metal oxides but the most common types of aerogels are silica, carbon and metal oxide aerogels. The process of synthesizing aerogel consists mainly of three stages; gelation, aging and drying. The process of drying aerogels affects the synthesized aerogel greatly as you can have three different types of aerogels by just using a different drying technique. Xerogel is one of the types of aerogels and it is achieved by drying aerogels at ambient pressure. This study aimed to design and develop a PVA/hydrocortisone loaded xerogel electrospun mat for topical drug delivery. The silica xerogel was synthesized using TMOS as a silica precursor, Ammonium hydroxide as a catalyst and Methanol as a co-solvent. The xerogel was ball-milled into fine powder and had its surface area, pore size and volume analyzed. In addition to that, hydrocortisone was loaded into three different samples; one consisting of only xerogel, the second of only PVA nanofibrous mat and the third consisting of both xerogel and PVA nanofibrous mat. In vitro drug release analysis was carried out for all of these samples. PVA was chosen for its biocompatible properties and stability. SEM and EDAX analyses were carried out to investigate the surface of the fibers and elements existing in the samples respectively. In addition to that, FTIR analysis was performed to identify the different materials making up the nanofibrous mats. The synthesized silica xerogel had a surface area of around 505 m²/g, pore size of around 3.8 nm and a pore volume of 0.48 cm³/g. SEM images showed the hydrocortisone loaded xerogel inside the PVA nanofibrous mat and the EDAX analysis confirmed the existence of silicone in the samples due to the existence of silica xerogel as well as a high concentration of Carbon due to hydrocortisone. The hydrocortisone loaded xerogel showed a slow sustained drug delivery release behavior and around 69.3% of the loaded hydrocortisone was released in 25 days. The PVA/xerogel/hydrocortisone nanofibrous mat showed a similar drug release behavior with a release of around 79.2% of the hydrocortisone initially loaded with PVA was released in just 30 minutes. Demonstrating a conventional or retarded drug release behavior. Meanwhile, the PVA/hydrocortisone electrospun mat showed a completely different drug release behavior. Around 98.55% of the hydrocortisone initially loaded into the PVA. In conclusion, Silica xerogel as a drug carrier was successfully synthesized. It was loaded with hydrocortisone. Hydrocortisone loaded silica xerogel drug release was investigated as well as PVA/xerogel/hydrocortisone and PVA/hydrocortisone. The result of these three different sample types were collected and compared. Both hydrocortisones loaded xerogel and PVA/xerogel/hydrocortisone showed a slow sustained drug release behavior. Meanwhile PVA/hydrocortisone showed a retarded drug release behavior. These results suggest the capability of PVA/hydrocortisone load xerogel mat to work as a sustained/controlled topical drug delivery carrier.