ENHANCED SOLUBILITY AND ANTIBIOFILM ACTIVITY OF RIFAMPICIN BY COMPLEXATION WITH β-CYCLODEXTRIN AND ARGININE

LONGHI MR; DAN CÓRDOBA AV; AIASSA V; ZOPPI A

Buenos Aires

Congreso; Reunion Conjunta de Sociedades de Biociencia; 2017

Biofilms are highly organized bacterial communities with functional heterogeneity that are formed on biotic and abiotic surfaces. They protect bacteria from the harsh external environment via self produced matrices of extracellular polymeric substances. They are also more resistant to antimicrobial agents than the same bacteria growing in a free swimming state. Rifampicin (RIF) is an antibiofilm antibiotic, which is able to attack the Staphylococci in biofilm, but the effectiveness of this drug is hampered by its limited solubility at neutral pH and variable bioavailability. The objective of this study was to improve the solubility and antibiofilm activity of RIF by multicomponent complex (MC) formation with β-cyclodextrin (β-CD) and Arginine (ARG). The inclusion ratio and binding constant were estimated from the phase-solubilitystudies (PSS). Complexes were prepared by the freeze-drying or physical mixturemethods, and then characterized by infrared spectrometry (IR), thermal analysis(TA), powder X-ray diffraction (XRD) and scanning electron microscopy (SEM).The minimum inhibitory concentration (MIC) was evaluated by the macrodilutionmethod according to CLSI indications. The effects of complexation against biofilms of Staphylococcus aureus resistant and sensible to methicillin (SAMR, SAMS)were assessed through the XTT reduction assay.The PSS demonstrated that the presence of β-CD and ARG produced asignificantly increase in RIF solubility. The TA and IR spectra of MC confirmed the molecular interactions between the components. SEM and XRD study showed thatthe MC was an amorphous solid. The MIC to RIF were 1 and 0.3 µg/ml to SAMRand SAMS, respectively. In biofilms, the MC caused a very significant reduction in cellular metabolic activity in both strains compared to free RIF.The MC developed in this work might be a promising system for oral drug delivery to treat bacterial infections.