title: Triclosan-loaded poloxamine micelles for enhanced topical antibacterial activity against biofilm.
abstract: Our research group is interested in the study of different technological approaches to treat hospital biofilm as a means to constrain nosocomial-acquired infections. The present work investigated the effect of the incorporation of the antibacterial agent triclosan (TS) into polymeric micelles of poloxamine T1107 (MW=15 kDa, 70 wt% PEO). The aggregation phenomenon was primarily investigated by means of Critical Micellar Concentration in a broad range of pH. Then, the effect of the polymer concentration on the micellar size was evaluated by Dynamic Light Scattering. Solubility levels increased up to 4 orders of magnitude. The drug inclusion affected the micellization, resulting in size increase and micellar fusion. This phenomenon was only apparent in TS-saturated systems. TS-loaded aggregates proved to be active in vitro against a broad spectrum of bacteria but more importantly, also against two representative clinical pathogens: methicilin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VREF). While the former was sensitive to even very low TS levels attainable in poloxamine-free aqueous media, the later was inhibited only when exposed to higher drug levels affordable exclusively using an inclusion system. These findings indicated the release of the drug from the reservoir. Finally, the activity of a TS-containing 5% poloxamine combination of pH 7.4 was assessed on biofilms of Staphylococcus epidermidis. Results showed a significant decrease (p<0.001) in the number of Colony-Formation Units when the biofilm was exposed to the TS/poloxamine as compared to the limited activity of the polymer-free TS control.
authors.affiliation: Department of Pharmaceutical Technology, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Chiappetta
authors.forename: José
authors.initials: J
authors.lastname: Degrossi
authors.forename: Sergio
authors.initials: S
authors.lastname: Teves
authors.forename: Miguel
authors.initials: M
authors.lastname: D'Aquino
authors.forename: Carlos
authors.initials: C
authors.lastname: Bregni
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sosnik
mesh_terms: D000891:Anti-Infective Agents, Local / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D003428:Cross Infection / Q000382:microbiology; D004355:Drug Stability; D013293:Enterococcus faecalis / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008027:Light; D016106:Methicillin Resistance; D008823:Micelles; D020442:Poloxamer / Q000737:chemistry; D012475:Salmonella / Q000187:drug effects; D012542:Scattering, Radiation; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects; D014260:Triclosan / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D020713:Vancomycin Resistance
chemical_list: D000891:Anti-Infective Agents, Local; D008823:Micelles; D020442:Poloxamer; D014260:Triclosan