METİSİLİNE DİRENÇLİ STAPHYLOCOCCUS AUREUS (MRSA) KAYNAKLI DERİ ENFEKSİYONLARIN TEDAVİSİ İÇİN TOPİKAL BİYOADEZİF JEL FORMÜLASYONLARININ GELİŞTİRİLMESİ

Abstract

In this study, it was aimed to develop a drug delivery system that will be applied topically in the treatment of skin infections caused by Methicillin-resistant S. aureus (MRSA), which has caused frequent infections in the community in the last decade together with resistance to antibiotics of Staphylococcus aureus (S. aureus), and will be used in human and veterinary fields in a way that will increase its effect especially against antimicrobial resistance and prevent the transmission of infection between each other within the scope of "One Health". There are other antimicrobials (phages, phage endolysins, etc.) and different formulation designs that increase the effect of antibiotics for the treatment of infections in the fight against antimicrobial resistance (AMR). In this thesis, it was aimed to develop a formulation for local application that will increase the effect of fusidic acid and its sodium salt (sodium fusidate), which have antimicrobial effects. In addition, gel formulations have been developed using chitosan, a bioadhesive biopolymer with antimicrobial properties, which contains a phage endolysin (LysSA10) synthesized as an alternative to antibiotics, along with a combination of antibiotic and endolysin. After characterization of the formulations, in vitro drug release, biocompatibility and antibacterial activity were examined. In vivo studies were conducted with the most suitable formulations and their effects were compared with commercial products in the MRSA-associated skin infection model in mice. As a result, a more effective, biocompatible drug system for topical application was developed, characterized by increased antibacterial activity against MRSA strains, ease of application, and sustained drug release in the target area.