Novel Nanoaggregates from Phoenix dactylifera (date palm) for Inhalational Management of Cystic Fibrosis Using Dry Powder Inhalers

Abstract

Purpose: Phoenix dactylifera extracts have shown efficacy as antioxidants and antibacterials for the treatment of lung diseases; however, the choice of route of administration remains a problem. The use of natural antibacterial remedies for the management of cystic fibrosis (CF) is promising due to recurring bacterial resistance to current antibiotics. Dry powder inhalers (DPIs) have also been identified as a patient-friendly, noninvasive method for local delivery of drugs to the lungs. Therefore, this work, which is the first of its kind, aimed to formulate nanoparticles of date palm extracts as DPIs and evaluate their aerodynamic and antibacterial biofilm characteristics for the potential treatment of CF. Method: Chitosan-based nanoparticles (CDN) comprising aqueous date fruit extract with increasing concentrations of chitosan (0.05, 0.1, and 0.2% w/v) were prepared. The in vitro aerosolization of the formulations was studied using a next-generation impactor (NGI), and good aerosolization profiles were achieved. The produced nanoparticles were characterized using FTIR and XRD to confirm physical properties and TEM and zeta sizer to confirm shape and size. The antimicrobial activity of CDN was evaluated using a Pseudomonas aeruginosa biofilm model cultured in an artificial sputum medium (ASM) mimicking cystic fibrosis conditions in the lungs. Results: Nanoparticles containing 0.05% w/v chitosan demonstrated the highest encapsulation efficiency (55.91%) and delivered the highest emitted dose (98.92%) and fine particle fraction (42.62%). CDN demonstrated the first-time-ever reported significant 3.3 log-cycle inhibition of P. aeruginosa biofilm cultured in ASM. TEM images revealed the formation of spherical particles with an average size of 42.98 ± 19.19 nm. FTIR and XRD studies demonstrated the compatibility of the components with the presence of the characteristic features of chitosan and date powder. Conclusions: This novel work showcases CDN as a prophylactic adjuvant for the management of cystic fibrosis using DPI.