Safety and effectiveness of sodium colistimethate-loaded nanostructured lipid carriers (SCM-NLC) against P. aeruginosa: in vitro and in vivo studies following pulmonary and intramuscular administration

Nanomedicine. 2019 Jun:18:101-111. doi: 10.1016/j.nano.2019.02.014. Epub 2019 Mar 6.

Abstract

The usefulness of nanotechnology to increase the bioavailability of drugs and decrease their toxicity may be a tool to deal with multiresistant P. aeruginosa (Mr-Pa) respiratory infections. We describe the preparation and the in vivo efficacy and safety of sodium colistimethate-loaded nanostructured lipid carriers (SCM-NLC) by the pulmonary and intramuscular routes. Nanoparticles showed 1-2 mg/L minimum inhibitory concentration against eight extensively drug-resistant P. aeruginosa strains. In vivo, SCM-NLC displayed significantly lower CFU/g lung than the saline and similar to that of the free SCM, even the dose in SCM-NLC group was lower than free SCM. There was no tissue damage related to the treatments. Biodistribution assessments showed a mild systemic absorption after nebulization and a notorious absorption after IM route. Altogether, it could be concluded that SCM-NLC were effective against P. aeruginosa in vivo, not toxic and distribute efficiently to the lung and liver after pulmonary or intramuscular administrations.

Keywords: Lipid nanoparticle; NLC; Pseudomonas aeruginosa; Sodium colistimethate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colistin / administration & dosage
  • Colistin / adverse effects
  • Colistin / analogs & derivatives*
  • Colistin / pharmacology
  • Drug Carriers / chemistry*
  • Female
  • Inflammation / pathology
  • Injections, Intramuscular
  • Lipids / chemistry*
  • Lung / microbiology*
  • Lung / pathology
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Nanostructures / chemistry*
  • Nanostructures / toxicity
  • Nanostructures / ultrastructure
  • Pseudomonas aeruginosa / drug effects*
  • Tissue Distribution / drug effects
  • Toxicity Tests
  • Treatment Outcome

Substances

  • Drug Carriers
  • Lipids
  • colistinmethanesulfonic acid
  • Colistin