Development of Novel Spray-dried Microparticles to Treat Cystic Fibrosis: A Tri-drug Approach

Abstract

Background: Cystic fibrosis is the predominant autosomal recessive disorder known to reduce life expectancy. Research findings indicate that around 60 to 70% of adult individuals with this condition carry infections of Pseudomonas aeruginosa.

Objective: The ongoing research investigates the potential synergy of merging ivacaftor and ciprofloxacin to address bacterial infections.

Methods: The two drugs were spray-dried into microparticles, which were then coated with Lsalbutamol and were to be delivered by a dry powder inhaler. Microparticles were generated by applying the spray drying method, utilizing bovine serum albumin and L-leucine in their preparation. Additionally, L-salbutamol was mixed and adsorbed onto the surface of the spray-dried microparticles, and it acted as a bronchodilator.

Results: The microparticles produced via spray drying exhibited a particle size measuring 1.6 ± 0.04 μm, along with a polydispersity ratio of 0.33. Their zeta potential measured -27.3 ± 1.1 mV, while the mass median aerodynamic diameter of these microparticles was 3.74 ± 0.08 μm. SEM, XRD, and FTIR studies confirmed the entrapment of ivacaftor and ciprofloxacin. The morphology was observed by SEM and TEM scans. Antibacterial synergy was confirmed through the agar broth and dilution method, and the formulation's safety was established based on the outcomes of the MTT assay.

Conclusion: Using spray-dried microparticles containing ciprofloxacin, ivacaftor, and L-salbutamol presents a novel approach to the treatment of cystic fibrosis.

Keywords: Dry powder inhaler; bovine serum albumin; leucine.; microparticles; polymeric drug delivery system; spray drying; targeted drug delivery.