Enhanced solubility and antibiofilm activity of rifampicin by complexation with B-cyclodextrin and arginine

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

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Biofilms are highly organized bacterial communities with functionalheterogeneity that are formed on biotic and abiotic surfaces.They protect bacteria from the harsh external environment via selfproduced matrices of extracellular polymeric substances. They arealso more resistant to antimicrobial agents than the same bacteriagrowing in a free swimming state. Rifampicin (RIF) is an antibiofilmantibiotic, which is able to attack the Staphylococci in biofilm, butthe effectiveness of this drug is hampered by its limited solubility atneutral pH and variable bioavailability. The objective of this studywas to improve the solubility and antibiofilm activity of RIF by multicomponentcomplex (MC) formation with β-cyclodextrin (β-CD) andArginine (ARG).The inclusion ratio and binding constant were estimated from thephase-solubility studies (PSS). Complexes were prepared by thefreeze-drying or physical mixture methods, and then characterizedby infrared spectrometry (IR), thermal analysis (TA), powderX-ray diffraction (XRD) and scanning electron microscopy (SEM).The minimum inhibitory concentration (MIC) was evaluated by themacrodilution method according to CLSI indications. The effects ofcomplexation against biofilms of Staphylococcus aureus resistantand sensible to methicillin (SAMR, SAMS) were assessed throughthe XTT reduction assay.The PSS demonstrated that the presence of β-CD and ARG produceda significantly increase in RIF solubility. The TA and IR spectraof MC confirmed the molecular interactions between the components.SEM and XRD study showed that the MC was an amorphoussolid. The MIC to RIF were 1 and 0.3 μg/ml to SAMR and SAMS,respectively. In biofilms, the MC caused a very significant reductionin cellular metabolic activity in both strains compared to free RIF.The MC developed in this work might be a promising system fororal drug delivery to treat bacterial infections.Keywords: rifampicin, multicomponent complex, antibiofilm activity,solubility