Development and assessment of countermeasure formulations for treatment of lung injury induced by chlorine inhalation

• Chlorine causes lung injury when inhaled and is considered a chemical threat agent.
• Countermeasures for treatment of chlorine-induced acute lung injury are needed.
• Formulations containing rolipram, triptolide, or budesonide were produced.
• Formulations with a wide range of release properties were developed.
• Countermeasure formulations inhibited chlorine-induced lung injury in mice.

Chlorine is a commonly used, reactive compound to which humans can be exposed via accidental or intentional release resulting in acute lung injury. Formulations of rolipram (a phosphodiesterase inhibitor), triptolide (a natural plant product with anti-inflammatory properties), and budesonide (a corticosteroid), either neat or in conjunction with poly(lactic:glycolic acid) (PLGA), were developed for treatment of chlorine-induced acute lung injury by intramuscular injection. Formulations were produced by spray-drying, which generated generally spherical microparticles that were suitable for intramuscular injection. Multiple parameters were varied to produce formulations with a wide range of in vitro release kinetics. Testing of selected formulations in chlorine-exposed mice demonstrated efficacy against key aspects of acute lung injury. The results show the feasibility of developing microencapsulated formulations that could be used to treat chlorine-induced acute lung injury by intramuscular injection, which represents a preferred route of administration in a mass casualty situation.