Study on the pulmonary delivery system of apigenin loaded albumin nanocarriers with antioxidant activity

Background: Respiratory diseases are mainly derived from acute and chronic inflammation of the alveoli and bronchi. The pathophysiological mechanisms of pulmonary inflammation mainly arise from oxidative damage that could ultimately lead to acute lung injury (ALI). Apigenin (Api) is a natural polyphenol with prominent antioxidant and anti-inflammatory properties in the lung. Inhalable formulations consist of nanoparticles (NPs) have several advantages over other administration routes therefore this study investigated the application of apigenin loaded bovine serum albumin nanoparticles (BSA-Api-NPs) for pulmonary delivery. Methods: Dry powder formulations of BSA-Api-NPs were prepared by spray drying and characterized by laser diffraction particle sizing, scanning electron microscopy, differential scanning calorimetry and powder X-ray diffraction. The influence of dispersibility enhancers(lactose monohydrate and L-leucine) on the in vitro aerosol deposition using a next generation impactor (NGI) was investigated in comparison to excipient-free formulation. The dissolution of Api was determined in simulated lung fluid by using Franz cell apparatus. The antioxidant activity was determined by 2,2-Diphenyl-1-picrylhydrazyl (DPPH˙) free radical scavenging assay. Results: The encapsulation efficiency and the drug loading was measured to be 82.61 ± 4.56% and 7.51 ± 0.415%. The optimized spray drying conditions were suitable to produce particles with low residual moisture content. The spray dried BSA-Api-NPs possessed good the aerodynamic properties due to small and wrinkled particles with low mass median aerodynamic diameter, high emitted dose and fine particle fraction. The aerodynamic properties was enhanced by leucine and decreased by lactose, however, the dissolution was reversely affected. The DPPH˙ assay confirmed that the antioxidant activity of encapsulated Api was preserved. Conclusion: This study provides evidence to support that albumin nanoparticles 49 are suitable carriers of Api and the use of traditional or novel excipients should be taken into consideration. The developed BSA-Api-NPs is a novel delivery system against lung injury with potential antioxidant activity

Drug Delivery Approaches for Apigenin: A Review

Apigenin is a naturally occurring plant flavone with prominent antioxidant and antiinflammatory properties. Although apigenin has the potential to be a promising molecule also for cancer treatment, its delivery to the body requires suitable dosage form design due to physicochemical characteristics that lead to poor bioavailability. It is classified as a BCS (Biopharmaceutical Classification System) II drug with low water solubility and high lipophilicity. Improving the solubility of apigenin is crucial, various formulation approaches have recently been employed e.g., nanocrystals have increased dissolution rate and antioxidant activity, while polymeric micelles increased the solubility to 148 times higher than that crude apigenin and showed enhanced cytotoxicity on hepatoma cells. PLGA encapsulated apigenin nanoparticles cause mitochondrial apoptosis and even DNA targeting could be achieved in skin cancer. The chapter reviews current approaches to the formulation of drug delivery systems containing apigenin