Aerosol of Enoximone/Hydroxypropyl-β-Cyclodextrin Inclusion Complex, Biopharmaceutical Evidence for ARDS...

Area of Science:

• Pulmonary pharmacology
• Drug delivery systems
• Respiratory medicine

Background:

• Phosphodiesterase (PDE) inhibitors, including enoximone (ENXM), show promise for treating pulmonary diseases like asthma, COPD, and ARDS.
• Current limitations exist for inhaled ENXM, particularly for conditions such as COVID-19 related ARDS (C-ARDS).

Purpose of the Study:

• To develop a novel, inhalable formulation of enoximone (ENXM) suitable for pulmonary administration.
• To create a nebulized solution of ENXM complexed with Hydroxypropyl-β-Cyclodextrin (HPβCD).

Main Methods:

• Development of an ENXM/HPβCD complex solution for nebulization.
• Characterization of the formulation's aerodynamic properties and biopharmaceutical features.
• In vitro evaluation using an air-liquid interface (ALI) lung cell model.

Main Results:

• The ENXM/HPβCD formulation demonstrated favorable aerosol droplet characteristics for bronchi-lung distribution.
• In vitro studies confirmed the formulation's ability to increase intracellular cyclic adenosine monophosphate (cAMP) levels.
• The formulation provided protection against oxidative stress in lung cells.

Conclusions:

• This research presents a significant advancement in optimizing enoximone (ENXM) delivery to the lungs.
• The developed ENXM/HPβCD formulation offers a promising therapeutic strategy for various pulmonary pathologies.