Nano/Mikro Yapılı Çok Bileşenli Ve Sıralı İlaç Salım Sistemlerinin Diyabetik Yaralardakı Etkisinin İncelenmesi

Abstract

Chronic wounds of patients with metabolic problems/diabetes, which are questioned by many researchers in the field of health and which have not yet been completely cured, are one of the challenging clinical problems. Vascular problems that develop in diabetic patients are the main cause of ischemia. On the other hand, deficiencies and impairments in cellular and humoral response develop in diabetic patients. For these reasons, the levels of growth factors that promote wound healing decrease or they lose their effective activity. Chronic wound healing problems develop in diabetic patients due to decreased cellular and humoral levels and blood supply problems due to vasculopathy added to them. Vascular endothelial growth factor (VEGF) (MA 45 kDa) is the most powerful angiogenic growth factor that stimulates vascularity during wound healing and thus accelerates healing. Granulocyte macrophage stimulating factor (GM-CSF) (MA 14 kDa) is known to stimulate cell proliferation and accelerate wound healing. Ensuring the presence of VEGF and GM-CSF levels in the wound area in a controlled manner or giving them indirectly will provide a positive biological effect on wound healing. The aim of this study is to develop a material consisting of PCL-based polymeric particles or polymer lipid hybrid particles loaded with VEGF and GM-CSF as biological dressing material in diabetic wounds. In the first stage, a temperature-sensitive, injectable, pluronic F127-based hydrogel containing angiogenic and cellular response-stimulating factors has been developed. The ability of these hydrogel, streptezotocin-induced diabetic Spraque Dawley rats to heal wounds created on the back was evaluated. Within the scope of the thesis, PCL-based polymeric particles and polymer-lipid hybrid particles (200-1000 nm) were prepared using the double emulsion solvent evaporation method. The particles were characterized by LS, AFM and SEM, and their size, size distribution and morphology were evaluated. In order to evaluate the in vitro uptake/release capabilities of polymeric and hybrid particles, bovine serum albumin (BSA, MA 60 kDa) and Lysozyme (MA 14 kDa) were used as model proteins. In the last of the studies, it was seen that polymer-lipid hybrid particles can be highly encapsulated proteins singly and/or bilaterally and that they can perform controlled releases of proteins according to their molecular weight for 21 days. The hybrid particles were then incorporated into the temperature-sensitive injectable Pluronic F127 hydrogel for topical application to the wound area. The rheological properties of the temperature-sensitive hydrogel were evaluated by determining the gelation temperature. Results showed that when the ambient temperature of the pluronic F127 gel was in a fluid state at +4 °C, it became a gel with an increase in viscosity when it increased to 37 °C (body temperature). With the in vitro release studies of the hydrogel, it was observed with the results obtained that the model protein-loaded hybrid particles minimized the undesired burst releases and performed the controlled releases. Within the scope of the study, the effect of the hydrogel containing VEGF/GM-CSF loaded polymer-lipid hybrid particles designed specifically for the wound area on the healing of 2 cm diameter wounds on the back of diabetic rats was monitored for 10 days as a preliminary study, and the wounds were examined histomorphically at the end of the period In this thesis, a carrier system that can perform multi-component sequential release and plays an active role in different phases of wound healing with the combination of VEGF and GM-CSF, which will take place for the first time in the literature, was designed and used. By encapsulating two active ingredients and by encapsulating the two active ingredients, this system has been made to be applied topically, and it has been questioned whether difficult-to-heal wounds heal faster by increasing inflammation in diabetic rats with controlled releases and then promoting angiogenesis.