Pulmonary delivered polymeric micelles – Pharmacokinetic evaluation and biodistribution studies

• Inhaled micelles achieved high lung retention and in vivo local sustained release.
• Inhaled micelles led to sustained uptake to the pulmonary vascular endothelium.
• Inhaled micelles efficiently translocated across air–blood barrier as intact vesicles.
• Inhaled micelles led to sustained distribution to the brain as intact vesicles.

Polymeric micelles represent interesting delivery systems for pulmonary sustained release. However, little is known about their in vivo release and translocation profile after delivery to the lungs. In the present study, curcumin acetate (CA), which is an ester prodrug of curcumin, or the mixture of CA and Nile red was encapsulated into PEG–PLGA micelles by a solvent evaporation method. The micellar formulation increased the stability of CA in water and physiologically relevant fluids and led to a sustained drug release in vitro. Following intratracheal (IT) administration to rats, CA loaded micelles achieved not only prolonged pulmonary retention with AUC values almost 400-fold higher than by IV route, but also local sustained release up to 24 h. In addition, IT delivery of micelles appeared to facilitate the uptake into the pulmonary vascular endothelium and efficiently translocate across the air–blood barrier and penetrate into the brain. Co-localization of CA and Nile red confirmed that micelles in lung and brain tissue were still intact. This study is the first to demonstrate that aerosolized PEG–PLGA micelles are a promising carrier for both pulmonary and non-invasive systemic sustained release of labile drugs.

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