title: Study on the Pulmonary Delivery System of Apigenin-Loaded Albumin Nanocarriers with Antioxidant Activity.
abstract: 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. Apigenin (Api) is a natural polyphenol with prominent antioxidant and anti-inflammatory properties in the lung. Inhalable formulations that consist of nanoparticles (NPs) have several advantages over other administration routes, and 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 was investigated in comparison to excipient-free formulation. The dissolution of Api was determined in simulated lung fluid by using the 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 were 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 aerodynamic properties due to small and wrinkled particles with low mass median aerodynamic diameter, high emitted dose, and fine particle fraction. The aerodynamic properties were 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.
  
  
  CONCLUSIONS
  This study provides evidence to support that albumin nanoparticles are suitable carriers of Api and the use of traditional or novel excipients should be taken into consideration. The developed BSA-Api-NPs are a novel delivery system against lung injury with potential antioxidant activity.
authors.affiliation: 1 Department of Pharmaceutics, Semmelweis University , Budapest, Hungary .
authors.forename: Zsófia Edit
authors.initials: ZE
authors.lastname: Pápay
authors.affiliation: 2 Department of Plant Anatomy, Institute of Biology, Eötvös Lóránd University , Budapest, Hungary .
authors.forename: Annamária
authors.initials: A
authors.lastname: Kósa
authors.affiliation: 2 Department of Plant Anatomy, Institute of Biology, Eötvös Lóránd University , Budapest, Hungary .
authors.forename: Béla
authors.initials: B
authors.lastname: Böddi
authors.affiliation: 3 Department of Pharmaceutics, UCL School of Pharmacy , London, United Kingdom .
authors.forename: Zahra
authors.initials: Z
authors.lastname: Merchant
authors.affiliation: 4 Formulation and Drug Delivery Research, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University , Liverpool, United Kingdom .
authors.forename: Imran Y
authors.initials: IY
authors.lastname: Saleem
authors.affiliation: 5 Department of Biomedical Science, Faculty of Science and Technology, University of Westminster , London, United Kingdom .
authors.forename: Mohammed Gulrez
authors.initials: MG
authors.lastname: Zariwala
authors.affiliation: 1 Department of Pharmaceutics, Semmelweis University , Budapest, Hungary .
authors.forename: Imre
authors.initials: I
authors.lastname: Klebovich
authors.affiliation: 3 Department of Pharmaceutics, UCL School of Pharmacy , London, United Kingdom .
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Somavarapu
authors.affiliation: 1 Department of Pharmaceutics, Semmelweis University , Budapest, Hungary .
authors.forename: István
authors.initials: I
authors.lastname: Antal
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000418:Albumins / Q000737:chemistry; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D047310:Apigenin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D008168:Lung / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010316:Particle Size; D014961:X-Ray Diffraction
chemical_list: D000336:Aerosols; D000418:Albumins; D000975:Antioxidants; D004337:Drug Carriers; D005079:Excipients; D016166:Free Radical Scavengers; D047310:Apigenin
keywords: aerosol distribution; flavonoid; inhaled therapy; modeling