Abstract
Widespread emergence of antibiotic-resistant pathogens in recent years has restricted the treatment options for various infectious diseases. Investigation of alternative antimicrobial agents and therapies is thus of utmost importance. Electrospinning of 50 mg/ml 2,3-dihydroxybenzoic acid (DHBA) into 24 % (w/v) poly(d,l-lactide) (PDLLA) and poly(ethylene oxide) (PEO) (1:1) produced nanofibers with an average diameter of 401 ± 122 nm. DHBA released from the nanofibers (315 ± 0.04 µg/ml within 2 h) inhibited the growth of Pseudomonas aeruginosa Xen 5, Klebsiella pneumoniae Xen 39, Escherichia coli Xen 14, Salmonella typhimurium Xen 26, and Staphylococcus aureus strains Xen 30, Xen 31, and Xen 36. The reason for the rapid diffusion of DHBA from PEO:PDLLA may be due to formation of hydrogen bonds between the hydroxyl groups of DHBA and the C=O groups of the PDLLA. DHBA formed a strong interaction with PDLLA and increased the thermal stability of the nanofiber mesh. The DHBA-containing nanofibers were non-hemolytic, suggesting that they may be incorporated in the development of a wound dressing.
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Jr Aduba DC, Hammer JA, Yuan Q, Yeudall WA, Bowlin GL, Yang H (2013) Semi-interpenetrating network (sIPN) gelatin nanofiber scaffolds for oral mucosal drug delivery. Acta Biomater 9:6576–6584
Andrews SC, Robinson AK, Rodriguez-Quinones F (2003) Bacterial iron homeostasis. FEMS Microbiol Rev 27:215–237
Baldwin SR, Simon RH, Boxer LA, Till GO, Kunkel RG (1985) Attenuation by 2,3-dihydroxybenzoic acid of acute lung injury induced by cobra venom factor in the rat. Am Rev Respir Dis 132:1288–1293
Blatt J, Taylor SR, Kontoghiorghes GJ (1989) Comparison of activity of deferoxamine with that of oral iron chelators against human neuroblastoma cell lines. Cancer Res 49:2925–2927
Bullen JJ, Rogers HJ, Spalding PB, Ward CG (2006) Natural resistance, iron and infection: a challenge for clinical medicine. J Med Microbiol 55:251–258
Burns JL, Mancoll JS, Phillips LG (2003) Impairments to wound healing. Clin Plastic Surg 30:47–56
Cason J Jr, Dyke GO (1950) Preparation of 2,3-dihydroxybenzoic acid. J Am Chem Soc 72:621–622
Che HL, Muthiah M, Ahn Y, Son S, Kim WJ et al (2011) Biodegradable particulate delivery of vascular endothelial growth factor plasmid from polycaprolactone/polyethylenimine electrospun nanofibers for the treatment of myocardial infarction. J Nanosci Nanotechnol 11:7073–7077
Chew SY, Wen J, Yim EKF, Leong KW (2005) Sustained release of proteins from electrospun biodegradable fibers. Biomacromolecules 6:2017–2024
Church D, Elsayed S, Reid O, Winston B, Lindsay R (2006) Burn wound infections. Clin Microbiol Rev 19:403–434
Eriksen TH, Skovsen E, Fojan P (2013) Release of antimicrobial peptides from electrospun nanofibres as a drug delivery system. J Biomed Nanotechnol 9:492–498
Frohbergh ME, Katsman A, Botta GP, Lazarovici P, Schauer CL et al (2012) Electrospun hydroxyapatite-containing chitosan nanofibers crosslinked with genipin for bone tissue engineering. Biomaterials 33:9167–9178
Gilchrist SE, Lange D, Letchford K, Bach H, Fazli L et al (2013) Fusidic acid and rifampicin co-loaded PLGA nanofibers for the prevention of orthopedic implant associated infections. J Control Release 170:64–73
Graziano JH, Grady RW, Cerami A (1974) The identification of 2,3-dihydroxybenzoic acid as a potentially useful iron-chelating drug. J Pharmacol Exp Ther 190:570–575
Graziano JH, Miller DR, Grady RW, Cerami A (1976) Inhibition of membrane peroxidation in thalassaemic erythrocytes by 2,3-dihydroxybenzoic acid. Br J Haematol 32:351–356
Heunis TDJ, Bshena O, Klumperman B, Dicks LMT (2011) Release of bacteriocins from nanofibers prepared with combinations of poly(d,l-lactide) (PDLLA) and poly(ethylene oxide) (PEO). Int J Mol Sci 12:2158–2173
Heunis TDJ, Dicks LMT (2010) Nanofibers offer alternative ways to the treatment of skin infections. J Biomed Biotechnol 61:1–10
Heunis TDJ, Smith C, Dicks LMT (2013) Evaluation of a nisin-eluting nanofiber scaffold to treat Staphylococcus aureus-induced skin infections in mice. Antimicrob Agents Chemother 57:3928–3935
Jin G, Prabhakaran MP, Nadappuram BP, Singh G, Kai D, Ramakrishna S (2012) Electrospun poly(l-lactic acid)-co-poly(ɛ-caprolactone) nanofibres containing silver nanoparticles for skin-tissue engineering. J Biomater Sci Polym Ed 23:861–871
Kenawy ER, Bowlin GL, Mansfield K, Layman J, Simpson DG et al (2002) Release of tetracycline hydrochloride from electrospun poly(ethylene-co-vinylacetate), poly(lactic acid), and a blend. J Control Release 81:57–64
Khalil KA, Fouad H, Elsarnagawy T, Almajhdi FN (2013) Preparation and characterization of electrospun PLGA/silver composite nanofibers for biomedical applications. Int J Electrochem Sci 8:3483–3493
Kim T, Lee H, Kim Y, Nam JM, Lee M (2013) Protein-coated nanofibers for promotion of T cell activity. Chem Commun 49:3949–3951
Kim K, Yu M, Zong X, Chiu J, Fang D et al (2003) Control of degradation rate and hydrophilicity in electrospun non-woven poly(d,l-lactide) nanofiber scaffolds for biomedical applications. Biomaterial 24:4977–4985
Mammadov R, Mammadov B, Guler MO, Tekinay AB (2012) Growth factor binding on heparin mimetic peptide nanofibers. Biomacromolecules 13:3311–3319
Manning CN, Schwartz AG, Liu W, Xie J, Havlioglu N et al (2013) Controlled delivery of mesenchymal stem cells and growth factors using a nanofiber scaffold for tendon repair. Acta Biomater 9:6905–6914
Meng ZX, Xu XX, Zheng W, Zhou HM, Li L et al (2011) Preparation and characterization of electrospun PLGA/gelatin nanofibers as a potential drug delivery system. Colloids Surf B 84:97–102
Mickova A, Buzgo M, Benada O, Rampichova M, Fisar Z et al (2012) Core/shell nanofibers with embedded liposomes as a drug delivery system. Biomacromolecules 13:952–962
Möllmann U, Heinisch L, Bauernfeind A, Köhler T, Ankel-Fuchs D (2009) Siderophores as drug delivery agents: application of the “Trojan Horse” strategy. Biometals 22:615–624
Payne SM (1994) Detection, isolation, and characterization of siderophores. Methods Enzymol 235:329–344
Rujitanaroj P, Pimpha N, Supaphol P (2008) Wound-dressing materials with antibacterial activity from electrospun gelatin fiber mats containing silver nanoparticles. Polymer 49:4723–4732
Sousa M, Ousingsawat J, Seitz R, Puntheeranurak S, Regalado A et al (2007) An extract from the medicinal plant Phyllanthus acidus and its isolated compounds induce airway chloride secretion: a potential treatment for cystic fibrosis. Mol Pharmacol 71:366
Torres NI, Noll KS, Xu S, Li J, Huang Q et al (2013) Safety, formulation and in vitro antiviral activity of the antimicrobial peptide subtilosin against herpes simplex virus type 1. Probiotics Antimicrob Prot 5:26–35
Vaxman F, Olender S, Lambert A, Nisand G, Grenier JF (1996) Can the wound healing process be improved by vitamin supplementation? Experimental study on humans. Eur Surg Res 28:306–314
Wang C, Yan KW, Lin YD, Hsieh PCH (2010) Biodegradable core/shell fibers by coaxial electrospinning: processing, fiber characterization, and its application in sustained drug release. Macromolecules 43:6389–6397
Wenk J, Foitzik A, Achterberg V, Sabiwalsky A, Dissemond J et al (2001) Selective pickup of increased iron by deferoxamine-coupled cellulose abrogates the iron-driven induction of matrix-degrading metalloproteinase 1 and lipid peroxidation in human dermal fibroblasts in vitro: a new dressing concept. J Invest Dermatol 116:833–839
Yu DG, Wang X, Li XY, Chian W, Li Y, Liao YZ (2013) Electrospun biphasic drug release polyvinylpyrrolidone/ethyl cellulose core/sheath nanofibers. Acta Biomater 9:5665–5672
Acknowledgments
Ahire JJ is grateful to Claude Leon Foundation Postdoctoral Fellowship (2013–2014), Cape Town, South Africa, for financial support.
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Ahire, J.J., Neppalli, R., Heunis, T.D.J. et al. 2,3-Dihydroxybenzoic Acid Electrospun into Poly(d,l-lactide) (PDLLA)/Poly(ethylene oxide) (PEO) Nanofibers Inhibited the Growth of Gram-Positive and Gram-Negative Bacteria. Curr Microbiol 69, 587–593 (2014). https://doi.org/10.1007/s00284-014-0635-3
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DOI: https://doi.org/10.1007/s00284-014-0635-3