ИСТИНА

Infections caused by intracellular pathogens are often difficult to treat due to the low activity of antibiotics against microbes that persist in phagocytic cells, such as Mycobacterium tuberculosis, M. Leprae, Brucella, Listeria, Salmonella . Delivery systems such as liposomes, micro / nanoparticles, lipid systems and conjugates may to contribute to increasing the therapeutic efficacy of antibiotics and antifungal agents by intracellular microorganisms. Considering the huge financial investments associated with the introduction of a new antibiotic into the market and the limited lifespan of antibiotics associated with the rapid development of bacterial resistance, the development of intracellular antibiotic delivery systems to increase their activity and reduce dosage and frequency of administration is currently an urgent task. The fluoroquinolones are a family of broad spectrum, systemic antibacterial agents that have been used widely as therapy of respiratory, abdominal and urinary tract infections, that recommended for treatment of tuberculosis caused by multiresistant strains of MT. Scientific team under the direction of Dr.Sc. Gelperina S.E. showed that polymeric nanoparticles consderably enhance the pharmacological effect of antibiotics of various classes, such as ansamycines, fluoroquinolones and aminoglycosides - by increasing their concentration in target organs. Thus binding of moxifloxacin to the PBCA nanoparticles enhanced its activity against experimental tuberculosis in mice. This phenomenon is most probably due to the better penetration and longer retention of moxifloxacin in the infected macrophages. Today commercial nano-sized formulation of moxifloxacin, as well as other antibiotics, does not exist. The actual tasks are the evaluation of the influence of the physicochemical properties of nanoparticles (size, surface charge,vector) on the rate of their capture and retention by macrophages. The purpose of this study is to develop approaches to the development and standardization of the nano-sized formulation of moxifloxacin based on the biodegradable and biocompatible polymeric nanoparticles (PBCA, PLA, PLGA) with the purpose to increase the efficacy of this antibiotic against intracellular infections. Methods of preparation of polymeric nanoparticles with optimisation of the techniques using multifactorial design; methods of analysis of physicochemical parameters of NPs (size and size distribution , zeta-potential, morphology and surface properties, molecular mass of the polymer); analysis of drug loading and encapsulation efficacy, drug release; analysis of biological properties: methods for evaluating antibacterial activity in vitro, study of hematotoxicity and hemocompatibility; study of the nanoparticles uptake by phagocytes, will used to develop and study the nano-sized formulation of moxifloxacin. Expected results: Development and standardization of the nanoparticulate formulation of moxifloxacin with improved efficacy against intracellular infections. Identification of the physicochemical parameters that might exert influence on the uptake and retention of Mox-loaded NPs in macrophages.