Aerosol delivery of ferulic acid-loaded nanostructured lipid carriers: A promising treatment approach against the respiratory disorders

Introduction: Treatment of lung diseases is one of the major healthcare challenges. Ferulic acid (FA), a phenolic compound with well-established antioxidant and anti-inflammatory properties, has shown promising therapeutic potential against the pulmonary disorders; however, low bioavailability may negatively affect its efficiency. This, prompted us to incorporate FA into the nanostructured lipid carriers (FA-NLCs) and evaluate the toxicity of this nanoformulation in human lung adenocarcinoma cell line (A549) and its suitability for pulmonary drug delivery. Methods: FA-NLCs were prepared by high-pressure homogenization followed by assessment of the physicochemical properties of nanoparticles, in vitro release profile, aerosol characteristics, in vitro cytotoxicity, pharmacokinetic parameters and lung deposition of the nanoparticles after nebulization in Balb/c mice. Results: Formation of FA-NLCs which exhibited a controlled release profile, was confirmed by scanning electron microscope and differential scanning calorimetry. FA-NLCs exhibited toxic effects on A549 cells for longer time periods as compared to FA solution. Following the aerosolization, suitable aerodynamic properties were obtained and FA-NLCs formulation provided significantly increased residence time and slower lung clearance for FA. Further confocal microscopy visualization confirmed the lung deposition of nanoparticles. Encapsulation of FA into the NLCs resulted in the improved pharmacokinetic parameters in plasma or lung tissue samples. Conclusion: Application of the aerosolized FA-NLCs formulation which improves the pulmonary bioavailability of FA might result in the increased efficiency and reduced dosing frequency of this phytochemical. In this respect, development of inhalable nano-based drug delivery systems appears as a promising therapeutic approach against the lung disorders.