Efficient Interfacially Driven Vehiculization of Corticosteroids by Pulmonary Surfactant

Area of Science:

• Pulmonary physiology and drug delivery
• Surface chemistry and biophysics

Background:

• Pulmonary surfactant stabilizes the lung's air-liquid interface.
• Surfactant's potential for targeted lung drug delivery is recognized but poorly understood.
• Key mechanisms of drug incorporation, surfactant performance impact, and long-distance drug transport remain unclear.

Purpose of the Study:

• To investigate pulmonary surfactant's ability to vehiculize corticosteroids (beclomethasone dipropionate [BDP] and budesonide [BUD]).
• To characterize corticosteroid incorporation into natural and synthetic surfactants.
• To assess the impact of corticosteroids on surfactant functionality and air-liquid interface distribution.

Main Methods:

• Comparison of a purified natural surfactant, Poractant alfa (natural), and CHF5633 (synthetic) surfactant.
• Characterization of corticosteroid (BDP, BUD) incorporation into surfactants.
• Evaluation of surfactant film formation, surface tension reduction, and compression-expansion cycling mimicking breathing.

Main Results:

• Natural and clinical surfactants incorporated corticosteroids up to 10% by mass.
• Corticosteroids did not impair surfactant's adsorption or ability to reach low surface tensions (<2 mN/m).
• Surfactant-corticosteroid combinations facilitated efficient drug diffusion along the air-liquid interface, surpassing liposome/micellar emulsion delivery.

Conclusions:

• Pulmonary surfactant effectively incorporates and maintains functionality with corticosteroids.
• Surfactant systems demonstrate superior ability to distribute corticosteroids along the air-liquid interface compared to current inhalation formulations.
• This highlights surfactant's potential as an advanced drug delivery vehicle for lung therapeutics.