Bioadhesive hydrogel as vehicle of a porphyrin for photosensitized inactivation of antibiotic-resistant P. aeruginosa

CAMPAGNO, LUCIANA PAULA; ALOVERO, FABIANA L.; MANZO RUBEN H.

Rosario

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

Facultad de Bioquímica y Farmacia. Universidad Nacional de Rosario

Photodynamic antimicrobial chemotherapy (PACT) utilize the ability of photosensitizers, in combination with visible light and molecular oxygen, to kill microbial cells and was proposed as an alternative for localized infections. Previously, we demonstrated that 5,10,15,20-tetra(4-N-methylpyridyl)porphyrin (TMPyP4+) is effective for photodynamic inactivation of P. aeruginosa. Among the various infections caused by P. aeruginosa, the eyes and ears are included as well as skin and soft tissue, infected burn wounds and diabetic foot ulcers. Topical application of a photosensitizer followed by irradiation is a viable application due to the accessibility of the target site. However, it is virtually impossible to keep a liquid vehicle in place on the skin for any reasonable time period. So, effective delivery methods for photosensitizer to the site of action are necessary.Carbomers are synthetic polymer of acrylic acid cross-linked with allylsucrose well established as a good bioadhesive and extensively investigated in pharmaceutical field.Our group have experience in the design of hydrogels for topical drug delivery. The aim of this study was the design and evaluation of Carbomer hydrogels as delivery platform ofthe cationic porphyrin TMPyP4+for the photoinactivation of multidrug-resistant P.aeruginosa. Hydrogels Carbomer 974 (range 0.1-0.4%) partially neutralized with NaOH were prepared and TMPyP4+ (5 and 10 mM) was added. Some dilutions in PBS were made for determination of bacterial photoinactivation by killing curve method.The hydrogels exhibit pH range 5.6-7.0, pseudoplastic flow, are stable and produce photoinactivation of P.aeruginosa. Slight delay in removing inoculum (~ 106 CFU/mL) with increasing viscosity of the hydrogel-TMPyP4+ was observed in comparison to a free solution TMPyP4+. However, no viable bacteria were detected in culture treated with hydrogel-TMPyP4+ at the higher Carbomer concentration after 60 min of irradiation with visible light (fluence rate: 28.7mW/cm2). This may partly be explained by the inherent viscosity of these hydrogels and low drug loading, leading to a reduced concentration gradient driving diffusion. Furthermore, is also likely that electrostatic binding of TMPyP4+ molecules by the negative polyelectrolyte had an influence on drug release. The known strategy for drug delivery using the concept of mucoadhesion would allow prolonging the residence time in the administration site. Hence, these hydrogels could be used in the development of an alternative and effective formulation for treatment for localized bacterial infections mediated by a photosensitized cationic porphyrin in response to the problem of antibiotic resistance.