Treatment of Francisella infections via PLGA- and lipid-based nanoparticle delivery of antibiotics in a zebrafish model

Dis Aquat Organ. 2017 Jun 19;125(1):19-29. doi: 10.3354/dao03129.

Abstract

We tested the efficiency of 2 different antibiotics, rifampicin and oxolinic acid, against an established infection caused by fish pathogen Francisella noatunensis ssp. orientalis (F.n.o.) in zebrafish. The drugs were tested in the free form as well as encapsulated into biodegradable nanoparticles, either polylactic-co-glycolic acid (PLGA) nanoparticles or nanostructured lipid carriers. The most promising therapies were PLGA-rifampicin nanoparticles and free oxolinic acid; the PLGA nanoparticles significantly delayed embryo mortality while free oxolinic acid prevented it. Encapsulation of rifampicin in both PLGA and nanostructured lipid carriers enhanced its efficiency against F.n.o. infection relative to the free drug. We propose that the zebrafish model is a robust, rapid system for initial testing of different treatments of bacterial diseases important for aquaculture.

Keywords: Antibiotics; Danio rerio; Francisella orientalis; Infection; Nanoparticles; Zebrafish embryo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Fish Diseases / drug therapy
  • Fish Diseases / microbiology*
  • Francisella
  • Gram-Negative Bacterial Infections / veterinary*
  • Lactic Acid / chemistry*
  • Lipids / chemistry*
  • Nanoparticles / chemistry*
  • Oxolinic Acid / administration & dosage
  • Oxolinic Acid / therapeutic use
  • Polyglycolic Acid / chemistry*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rifampin / administration & dosage
  • Rifampin / therapeutic use
  • Zebrafish

Substances

  • Anti-Bacterial Agents
  • Lipids
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Oxolinic Acid
  • Rifampin