Inhalable resveratrol microparticles produced by vibrational atomization spray drying for treating pulmonary arterial hypertension

The rare disorder pulmonary arterial hypertension is characterized by elevated pulmonary arterial pressure and right heart failure. Currently, the treatments have improved, but a cure has not yet been discovered. In this study, we developed a new formulation using an innovative controlled delivery system for resveratrol: s dry powder inhaler form designed for pulmonary administration. The particles were composed of resveratrol, as the therapeutic agent; poly(ε-caprolactone), for structuring the controlled-release matrix; sodium deoxycholate, to prevent agglomeration; and trehalose, as drying adjuvant, respectively. The particles were obtained using the piezoelectric atomization technique with a Nano Spray Dryer B-90®. The fine particle fraction was approximately 50% and the theoretical aerodynamic diameter was 2.32 μm. The process afforded excellent yields (approximately 80%) with low powder moisture (less than 2.0%). Due to the low density and the increased flowability of the powder, the spherical shape of the particles and an irregular surface, the microparticles possessed aerodynamic properties suitable for drug deposition on the bronchial and alveolar regions of the lungs. The aerodynamic properties and in vitro sustained release profiles showed a great potential for the inhaled administration of drugs such as resveratrol suitable for the treatment of pulmonary arterial hypertension.

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