title: Preparation and biological evaluation of ethionamide-mesoporous silicon nanoparticles against Mycobacterium tuberculosis.
abstract: Ethionamide (ETH) is an important second-line antituberculosis drug used for the treatment of patients infected with multidrug-resistant Mycobacterium tuberculosis. Recently, we reported that the loading of ETH into thermally carbonized-porous silicon (TCPSi) nanoparticles enhanced the solubility and permeability of ETH at different pH-values and also increased its metabolization process. Based on these results, we synthesized carboxylic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs) conjugated with ETH and its antimicrobial effect was evaluated against Mycobacterium tuberculosis strain H37Rv. The activity of the conjugate was increased when compared to free-ETH, which suggests that the nature of the synergy between the NPs and ETH is likely due to the weakening of the bacterial cell wall that improves conjugate-penetration. These ETH-conjugated NPs have great potential in reducing dosing frequency of ETH in the treatment of multidrug-resistant tuberculosis (MDR-TB).
authors.affiliation: UCIBIO/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal. Electronic address: nuno.vale@fc.up.pt.
authors.forename: Nuno
authors.initials: N
authors.lastname: Vale
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Correia
authors.affiliation: UCIBIO/REQUIMTE, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 687, 4169-007 Porto, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Silva
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Figueiredo
authors.affiliation: Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014, Finland.
authors.forename: Ermei
authors.initials: E
authors.lastname: Mäkilä
authors.affiliation: Laboratory of Industrial Physics, Department of Physics and Astronomy, University of Turku, FI-20014, Finland.
authors.forename: Jarno
authors.initials: J
authors.lastname: Salonen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Jouni
authors.initials: J
authors.lastname: Hirvonen
authors.affiliation: Microbiology and Infection Research Domain, Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
authors.forename: Jorge
authors.initials: J
authors.lastname: Pedrosa
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
authors.forename: Hélder A
authors.initials: HA
authors.lastname: Santos
authors.affiliation: Microbiology and Infection Research Domain, Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Fraga
mesh_terms: D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D005000:Ethionamide / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D016062:Porosity; D012825:Silicon / Q000737:chemistry*; D012995:Solubility; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D005000:Ethionamide; D012825:Silicon
keywords: Ethionamide; MIC(50); Mycobacterium tuberculosis; Porous silicon nanoparticles; Strain H37Rv