POLYMERIC PARTICLES OF CHITOSAN LOADED WITH POLYMYXIN B: DEVELOPMENT AND STUDY OF ANTIBACTERIAL PROPERTIES
Antimicrobial activity; Encapsulation; Synergy; Broth microdilution; Chitosan; Polymyxin B; spray drying; Gram-negative bacteria.
Numerous infections are caused by Gram-negative bacteria in healthcare facilities such as hospitals and clinics. Many of these bacteria are already resistant to antibiotics traditionally used to combat them, resulting in few treatment options. This can further compromise the health and even the lives of patients who contract these infections, especially those hospitalized in Intensive Care Units (ICU). One of the causes of this increase in bacterial resistance to some classes of antibiotics is the indiscriminate and increased use of these types of antimicrobials. One very effective antibiotic for treating these bacteria is polymyxins (polymyxin E and polymyxin B). However, they can cause harmful side effects to the body. One way to enhance the antibacterial activity of antibiotics, reducing the amount needed and, consequently, reducing negative side effects, is to encapsulate them with polysaccharide compounds. Chitosan is an example of a polysaccharide compound that has been extensively researched and used in the pharmaceutical industry due to its biocompatibility, nontoxicity and, mainly, its intrinsic antimicrobial activity. The combination of antibiotics with chitosan can be performed by encapsulating the antibiotic in chitosan using the spray drying technique. In this context, the aim of this study was to produce chitosan particles incorporated with polymyxin B and to characterize their antimicrobial action against clinical strains of Gram-negative, multidrug-resistant (MDR) Klebsiella pneumoniae and Citrobacter freundii with resistance to polymyxin B. Additionally, physicochemical characterizations of the particles and precursor substances were performed by Scanning Electron Microscopy (SEM), Energy Dispersive X-ray (EDS), Thermogravimetric Analysis (TGA) and Fourier Transform Infrared Spectroscopy with Attenuated Total Reflection (FTIR-ATR), complemented by Principal Component Analysis (PCA). The broth microdilution test performed with chitosan microparticles incorporated with polymyxin showed the existence of synergy between the two materials, since they resulted in an efficient Minimum Inhibitory Concentration (MIC) against the two bacteria tested (Klebsiella pneumoniae and Citrobacter freundii), lower than that obtained for the pure materials. Based on these findings, it is possible to assume that the combination of chitosan with polymyxin B presents promising prospects for combating MDR Gram-negative bacteria and that further studies can be carried out to validate the clinical application of this associative potential.