Cationic polymer induces sensitization to the action of lytic agents in Pseudomonas aeruginosa without affecting Candida albicans

CORTI, MELISA BELÉN; ALOVERO, FABIANA L.; MANZO RUBEN H; SANCHEZ, MARIANA

Rosario

Congreso; 4° Reunión Internacional de Ciencias Farmacéuticas - RICIFA2016; 2016

Facultad de Bioquímica y Farmacia. Universidad Nacional de Rosario

Several cationic polymers can act as antimicrobials by themselves or deliver bioactive molecules. It is required a density of positive charges on the polymer to promote effective interactions with the negatively charged bacterial walls. Eudragit E100® (EuE) is a cationic polymer based on dimethylaminoethyl methacrylate and other neutral methacrylic acid esters. EuE aqueous dispersion exhibit enhanced bactericidal action of fluoroquinolones against Pseudomonas aeruginosa derived from outer-membrane permeabilization and bacterial membrane depolarization coupled with fluoroquinolone action.Compounds with nonspecific activities that also affect the integrity and function of the bacterial membrane must be evaluated for selective activity. Anti-yeast activity is one of the test commonly used to distinguish the membrane-active entities. The effect of EuE in P.aeruginosa and Candida albicans was compared by assessing sensitization to lytic agents and changes in viable count after a brief exposure to the polymer.EuE was partially neutralized with HCl (EuEClx, 30 and 50% of the equivalents: EuECl30 y EuECl50)to improve compatibility.Overnight culturesOD:0.5 wereadjusted in saline and incubated (10 min-37°C)with EuEClx (conc. range: 15-1250 µg/mL). After centrifugation, cells were treated with lytic agents, incubated (4 min-37°C) and the OD at 420 nm (P. aeruginosa) and 530 nm (C.albicans) were measured. Aliquots were distributed in MH agar and Cetrimide agar (P.aeruginosa) or Sabouraud agar (C.albicans) for viable count after polymer exposure.Sensitization to lytic agents concentration- and time-dependent was observed against P.aeruginosa, but does not affect yeast. Only had a limited effect at very high concentrations. Viability of C.albicans was not modified by EuEClx, while the viable account of P.aeruginosa was reduced. It was more pronounced after exposure to EuECl30, in which a greater proportion of positive charges is available. Furthermore, P.aeruginosa becomes sensitive to cetrimide, quaternary ammonium compound against which this bacterial species is resistant, adding further evidence that the polymer alters the impermeability of their external membrane.These results support the potential use of this cationic polymer for developing antimicrobial carrier systems and help optimize drug-carrier ratios, ensuring selective enhancement of antimicrobial action without potential effect on other cells.