Treatment of respiratory damage in mice by aerosols of drug-encapsulating targeted lipid-based particles

J Control Release. 2017 Jul 10:257:163-169. doi: 10.1016/j.jconrel.2016.03.039. Epub 2016 Apr 5.

Abstract

The purpose of this study was to develop a treatment for respiratory damage caused by exposure to toxic industrial chemicals (TICs), including mass casualty events, by aerosols of dexamethasone and/or N-acetyl cysteine formulated in targeted lipid-based particles. Good encapsulation, performance as slow-release drug depots, conservation of matter, and retention of biological activity were obtained for the three drug-carrier formulations, pre- and post-aerosolization. Weight changes over a 2week period were applied, deliberately, as a non-invasive clinical parameter. Control mice gained weight continuously, whereas a non-lethal 30minute exposure of mice to 300ppm Cl2 in air showed a two-trend response. Weight loss over the first two days, reversing thereafter to weight gain, but at a rate and level significantly slower and smaller than those of the control mice, indicating the chlorine damage was long-term. The weight changes of Cl2-exposed mice given the inhalational treatments also showed the two-trend response, but the weight gain rates and levels were similar to those of the control mice, reaching the weight-gain range of the control mice. Following this proof of concept, studies are now extended to include additional TICs, and biochemical markers of injury and recovery.

Keywords: Aerosols; Mass casualty events; Respiratory damage; TIC exposure.

MeSH terms

  • Acetylcysteine / administration & dosage*
  • Acetylcysteine / pharmacokinetics
  • Administration, Inhalation
  • Aerosols / chemistry*
  • Animals
  • Dexamethasone / administration & dosage*
  • Dexamethasone / pharmacokinetics
  • Drug Delivery Systems
  • Drug Liberation
  • Expectorants / administration & dosage*
  • Expectorants / pharmacokinetics
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / pharmacokinetics
  • Liposomes / chemistry*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Nebulizers and Vaporizers
  • Respiratory Tract Diseases / chemically induced
  • Respiratory Tract Diseases / drug therapy

Substances

  • Aerosols
  • Expectorants
  • Glucocorticoids
  • Liposomes
  • Dexamethasone
  • Acetylcysteine