title: Anti-biofilm activity of chitosan gels formulated with silver nanoparticles and their cytotoxic effect on human fibroblasts.
abstract: The development of multi-species biofilms in chronic wounds is a serious health problem that primarily generates strong resistance mechanisms to antimicrobial therapy. The use of silver nanoparticles (AgNPs) as a broad-spectrum antimicrobial agent has been studied previously. However, their cytotoxic effects limit its use within the medical area. The purpose of this study was to evaluate the anti-biofilm capacity of chitosan gel formulations loaded with AgNPs, using silver sulfadiazine (SSD) as a standard treatment, on strains of clinical isolates, as well as their cytotoxic effect on human primary fibroblasts. Multi-species biofilm of Staphylococcus aureus oxacillin resistant (MRSA) and Pseudomonas aeruginosa obtained from a patient with chronic wound infection were carried out using a standard Drip Flow Reactor (DFR) under conditions that mimic the flow of nutrients in the human skin. Anti-biofilm activity of chitosan gels and SSD showed a log-reduction of 6.0 for MRSA when chitosan gel with AgNPs at a concentration of 100 ppm was used, however it was necessary to increase the concentration of the chitosan gel with AgNPs to 1000 ppm to get a log-reduction of 3.3, while the SSD showed a total reduction of both bacteria in comparison with the negative control. The biocompatibility evaluation on primary fibroblasts showed better results when the chitosan gels with AgNPs were tested even in the high concentration, in contrast with SSD, which killed all the primary fibroblasts. In conclusion, chitosan gel formulations loaded with AgNPs effectively prevent the formation of biofilm and kill bacteria in established biofilm, which suggest that chitosan gels with AgNPs could be used for prevention and treatment of infections in chronic wounds. The statistic significance of the biocompatibility of chitosan gel formulations loaded with AgNPs represents an advance; however further research and development are necessary to translate this technology into therapeutic and preventive strategies.
authors.affiliation: Facultad de Ciencias Quimicas, Universidad Autonoma de San Luis Potosi, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Pérez-Díaz
authors.affiliation: Facultad de Ciencias Quimicas, Universidad Autonoma de San Luis Potosi, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Alvarado-Gomez
authors.affiliation: Servicio de Epidemiologia del Hospital Central "Dr. Ignacio Morones Prieto", San Luis Potosi, Mexico.
authors.forename: M
authors.initials: M
authors.lastname: Magaña-Aquino
authors.affiliation: Laboratorio de Biotecnologia, Instituto Nacional de Rehabilitacion, Mexico, D.F., Mexico.
authors.forename: R
authors.initials: R
authors.lastname: Sánchez-Sánchez
authors.affiliation: Laboratorio de Biotecnologia, Instituto Nacional de Rehabilitacion, Mexico, D.F., Mexico.
authors.forename: C
authors.initials: C
authors.lastname: Velasquillo
authors.affiliation: Facultad de Ciencias Quimicas, Universidad Autonoma de San Luis Potosi, Mexico.
authors.forename: C
authors.initials: C
authors.lastname: Gonzalez
authors.affiliation: Division de Estudios de Posgrado (Tecnologia Farmaceutica), Facultad de Estudios Superiores Cuautitlan, Universidad Nacional Autonoma de Mexico, Cuautitlan Izcalli, Estado de Mexico, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Ganem-Rondero
authors.affiliation: Doctorado en Ciencias Odontológicas Facultad de Estomatologia, UASLP, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Martínez-Castañon
authors.affiliation: Doctorado en Ciencias Odontológicas Facultad de Estomatologia, UASLP, Mexico.
authors.forename: N
authors.initials: N
authors.lastname: Zavala-Alonso
authors.affiliation: Facultad de Ciencias Quimicas, Universidad Autonoma de San Luis Potosi, Mexico.
authors.forename: F
authors.initials: F
authors.lastname: Martinez-Gutierrez
mesh_terms: D018441:Biofilms / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D005347:Fibroblasts / Q000187:drug effects; D005782:Gels; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D012834:Silver / Q000737:chemistry* / Q000633:toxicity
chemical_list: D005782:Gels; D012834:Silver; D048271:Chitosan
keywords: Biofilm; CDC reactor; Chitosan; Chronic wound infection; DFR reactor; Primary fibroblasts; Pseudomonas aeruginosa; Silver nanoparticles; Staphylococcus aureus