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Clavanin bacterial sepsis control using a novel methacrylate nanocarrier.

Abstract
Controlling human pathogenic bacteria is a worldwide problem due to increasing bacterial resistance. This has prompted a number of studies investigating peptides isolated from marine animals as a possible alternative for control of human pathogen infections. Clavanins are antimicrobial peptides isolated from the marine tunicate Styela clava, showing 23 amino acid residues in length, cationic properties, and also high bactericidal activity. In spite of clear benefits from the use of peptides, currently 95% of peptide properties have limited pharmaceutical applicability, such as low solubility and short half-life in the circulatory system. Here, nanobiotechnology was used to encapsulate clavanin A in order to develop nanoantibiotics against bacterial sepsis. Clavanin was nanostructured using EUDRAGIT(®) L 100-55 and RS 30 D solution (3:1 w:w). Atomic force, scanning electron microscopy and dynamic light scattering showed nanoparticles ranging from 120 to 372 nm in diameter, with a zeta potential of -7.16 mV and a polydispersity index of 0.123. Encapsulation rate of 98% was assessed by reversed-phase chromatography. In vitro bioassays showed that the nanostructured clavanin was partially able to control development of Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Furthermore, nanostructures did not show hemolytic activity. In vivo sepsis bioassays were performed using C57BL6 mice strain inoculated with a polymicrobial suspension. Assays led to 100% survival rate under sub-lethal sepsis assays and 40% under lethal sepsis assays in the presence of nanoformulated clavanin A until the seventh day of the experiment. Data here reported indicated that nanostructured clavanin A form shows improved antimicrobial activity and has the potential to be used to treat polymicrobial infections.
AuthorsAmanda C M Saúde, Alicia S Ombredane, Osmar N Silva, João A R G Barbosa, Susana E Moreno, Ana Claudia Guerra Araujo, Rosana Falcão, Luciano P Silva, Simoni C Dias, Octávio L Franco
JournalInternational journal of nanomedicine (Int J Nanomedicine) Vol. 9 Pg. 5055-69 ( 2014) ISSN: 1178-2013 [Electronic] New Zealand
PMID25382976 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Drug Carriers
  • Methacrylates
  • clavanin A
Topics
  • Animals
  • Anti-Bacterial Agents (administration & dosage, chemistry)
  • Antimicrobial Cationic Peptides (administration & dosage, chemistry, isolation & purification)
  • Bacteremia (drug therapy)
  • Bacteria (drug effects)
  • Blood Proteins (administration & dosage, chemistry)
  • Cell Line, Tumor
  • Drug Carriers (administration & dosage, chemistry)
  • Methacrylates (administration & dosage, chemistry)
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles (administration & dosage, chemistry)
  • Nanotechnology
  • Urochordata (chemistry)

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