Development and characterization of nanofibrous structures for atopic dermatitis treatment

Abstract

Atopic dermatitis (AD) is a chronic, itchy, and inflammatory skin disease that causes dry skin, rashes, and inflammation. Since AD has no definitive treatment so far, moisturizers and softening creams are used to control the disease, whose severity changes periodically; Topical or oral anti-inflammatory drugs and systemic corticosteroids are applied to control exacerbations and to minimize the risk of infection by relieving itching. However, since long-term use of synthetic drugs causes many side effects, it is not recommended for young children and infants, who make up the majority of people suffering from this disease. For this reason, various complementary treatments such as hydrogels, wet dressings or natural oil-added wound dressings have been developed as an alternative to drug therapy. Wound dressings are structures that protect the wounds against various bacteria and infections, support cell proliferation in the injured area, provide the necessary oxygen circulation for the skin, and at the same time maintain the moisture balance of the wound environment. These structures can be woven fabrics (gauze), hydrogels or nanofiber surfaces. Wound dressings can be made functional by adding therapeutic agents on or inside the structure of dressings. When therapeutic agents are added to the surface of dressings post-production, they cannot be released efficiently. In order to achieve sustained release, additives must be trapped in the fibers by different methods during the fiber production phase. Thus, it is possible to adjust the dosage of therapeutic agents and transfer them to the skin surface in a controlled manner according to the healing process. For this reason, studies on nanofiber wound dressings produced by electrospinning method have increased in recent years. Electrospinning is a widely used fiber spinning method for the preparation of nanofibers, versatile and easily adaptable to different materials. Electrospinning apparatus consists high voltage source, conductive polymer solution, syringe, syringe pump, needle/nozzle and collector plate. While the conductive polymer solution, which is fed from the pump and comes to the syringe tip, is drawn from one pole to the other by the electric field effect between the collector plate and the syringe tip, while the solvent in the polymer is removed just before it reaches the collector, and the polymer solidifies, accumulating on the collector plate in the form of nano or micro-sized fibers, forming a nanofiber surface. In electrospinning; Solution or polymer properties, the distance between the needle tip and the collector (collector plate), the amount of applied voltage, the collector movement or environmental factors such as humidity, pressure and temperature are the parameters that affect the nanofiber structure. There are three different electrospinning methods commonly used for the controlled release properties of electrospinning surfaces. These are blend electrospinning, emulsion electrospinning and coaxial electrospinning. Two methods whose sustained release properties can be compared among these three methods are emulsion and coaxial electrospinning. Because the fibers produced by the blend electrospinning method do not show continuous release by making burst release. In the emulsion electrospinning method, the oil phase and the aqueous phase form an emulsion with the help of surfactant added to the polymer solution, and fibers are produced with a single nozzle electrospinning mechanism. With this method, it is possible to encapsulate the additives in the fiber and provide continuous release. The fibers produced by the coaxial electrospinning method are in the core-shell structure. Therefore, sustained release for a long time can be achieved. The nozzle used to obtain this structure has two separate needles, one in the center of the other. Essential oils (EOs) are oils extracted from plants that contain a variety of complex chemical compounds. Since prehistoric times, EOs have been widely used for a variety of medicinal purposes, including antibacterial, antiviral, insecticidal, and analgesic and anti-inflammatory. Because many EOs are volatile by nature, encapsulating oils into the fiber is a cost-effective way to protect them from evaporation and oxidation while also controlling their release. Thyme oil (TEO) used in this study shows high antibacterial activity thanks to components such as thymol and carvacol. Since S.aureus colonization accumulating on the skin surface in AD disease causes exacerbation of the disease, the production of nanofibers containing TEO has been considered as a solution to this problem. On the other hand, Hypericum Perforatum oil (HPO), which has been approved by the literature to contribute to wound healing by supporting cell proliferation thanks to its components such as hypericisin and hyperforin, was chosen as another nanofiber additive. Finally, nanofibers were produced with Borage oil (BO) with the highest Gamma Linolenic acid (GLA) content, which is one of the essential fatty acids that cannot be synthesized in the bodies of patients with AD due to the deficiency of the δ-6-desaturase enzyme. GLA is an important component in AD patients in terms of preventing water loss in the skin and protecting the barrier functions of the skin. In addition to additives, it is also important to use biocompatible and biodegradable polymers in nanofiber production due to their low toxicity and mimicry of the skin's extracellular matrix (ECM). Examples of these polymers are polyvinylalcohol (PVA), polycaprolactone (PCL), polyvinylprolidone (PVP) used in the thesis. In this study, it was aimed to obtain essential oil loaded (hypericum perforatum oil, thyme oil and borage oil) nanofiber structures using emulsion and coaxial electrospinning methods using PVA, PCL and PVP polymers. The effects of the variables on nanofiber structures were evaluated by changing parameters such as polymer type, polymer concentration, essential oil type, essential oil ratio, surfactant type and surfactant ratio. In addition to the production and characterization tests of nanofibrous structures, the antibacterial properties of TEO-containing samples were investigated. Firstly, nanofibers were produced by emulsion electrospinning method using hydrophilic PVA polymer and HPO. The effects of increasing amounts of surfactant used for emulsion formation in the prepared solutions on fiber morphology were observed. Then, emulsion nanofibers were produced with hydrophilic polymers PVP and hydrophobic PCL polymers separately. This time, the amount of surfactant was kept constant and the effects of the increased amount of oil on the fiber structure were examined. After studies on the effect of oil and surfactant in emulsion electrospinning method, nanofibers were produced from PVP/PCL polymers at different rates for the optimization of coaxial nanofibers. The morphologies of the produced fibers were examined, the hydrophilicity/hydrophobicity test was performed on the surfaces and the effect of polymer ratios on the surface properties was investigated. As a result of the studies, the most suitable polymer ratio was determined for oil loading. Oil-loaded fiber productions were made by adding TEO, BO and TEO:BO (1:1 v/v mixture) to the PVP polymer, which will form the core structure of the fiber in coaxial fibers. The results of SEM images, fiber diameter distributions, FTIR and antibacterial activity tests of the produced samples were analyzed and interpreted. Finally, oil-loaded nanofibers with a hydrophobic PCL polymer core/shell structure were produced. While the shell polymer solution was kept constant at 10% wt PCL, the core polymer solution was prepared at 10% wt PCL and 8% wt PCL. TEO and TEO:BO mixed oils were added to the core solutions as oil additives. The obtained nanofibers were evaluated in terms of fiber morphology and surface hydrophilicity, the connections between the viscosity and conductivity values of the solutions and fiber structures were explained, and suggestions for future studies were presented.