Development of an erythromycin-trypsin combination treatment for biofilm infections

• Main Author: Martin Janczewski 1996-
• Other Authors: Háskóli Íslands
• Format: Thesis
• Language: English
• Published: 2022
• Subjects: Lyfjafræði; Örverur; atlantic cod
• Online Access: http://hdl.handle.net/1946/40672

A biofilm describes a colony of bacteria forming a multicellular structure. It represents the main mode of growth for bacterial life on earth and is common in human bacterial infections. Biofilm formation results in lowered susceptibility to antibiotics and increased difficulty of infection treatment. Trypsin derived from Atlantic cod demonstrates a high effectiveness in biofilm disruption, it’s extractability from fishing by-products also make it both an economical and environmentally agreeable choice for pharmaceutical use. Therefore, an antibiotic-trypsin combination therapy could be used to treat biofilm infections more effectively than medical therapy using antibiotics alone. Erythromycin, an antibiotic of the macrolide class, has shown compatibility in formulations containing trypsin without diminishing the enzyme’s activity, making it the main candidate for such a formulation. The main obstacle with its use is the drugs low solubility. In this research erythromycin’s solubility enhancement in Penzim® lotion with the surfactants Span 83, Span 85, and Tween 40, was investigated. Synergistic interactions between these surfactants were observed, allowing for higher solubilization of erythromycin than previously observed with surfactants. Several formulations routinely measured erythromycin solubility exceeding 10 mg/ml. The highest achieved erythromycin concentration was measured in a formulation using 3.33% w/v of Span 83, 1.11% w/v of Span 85, and 3.33% w/v of Tween 40. Enzyme activity tests showed an increase in the stability of trypsin’s activity in formulations containing surfactants, when compared to pure Penzim®. Erythromycin stability studies showed a mild decrease in erythromycin concentration over time for the tested formulations, with a larger decrease for samples stored at 40°C than at 25°C. The creation of trypsin formulations reaching high levels of erythromycin solubility without a significant loss in enzymatic activity is a major advance for the development of an erythromycin-trypsin treatment ...