Novel therapeutic approach for the treatment of cystic fibrosis based on freeze-dried tridrug microparticles to treat cystic fibrosis.

Background: Cystic fibrosis is a severe, autosomal recessive disease that shortens life expectancy. According to studies, approximately 27% of patients with CF aged 2-5 years and 60 to 70% of adult patients are infected with P. aeruginosa. The patients experience bronchospasm leading to a persistent contracted state of the airways.

Objectives: The current work explores the possibility of combining ivacaftor and ciprofloxacin to combat the bacteria. A third drug L-salbutamol would be coated onto the surface of the drug-entrappped microparticles to instantaneously provide relief from bronchoconstriction.

Methods: The microparticles were prepared using bovine serum albumin and L-leucine using the freeze-drying approach. The process and formulation parameters were optimized. The prepared microparticles were surface coated by L-salbutamol using the dry-blending method. The microparticles were subjected to rigorous in-vitro characterization for entrapment, inhalability, antimicrobial activity, cytotoxicity study and safety. The performance of the microparticles to be loaded into a inhaler was checked by the Anderson cascade impactor.

Results: The freeze-dried microparticles had a particle size of 817.5 ± 5.6 nm with a polydispersity ratio of 0.33. They had a zeta potential of -23.3 ± 1.1 mV. The mass median aerodynamic diameter of the microparticles was 3.75 ± 0.07 μm, and the geometric standard diameter was 1.66 ± 0.033 μm. The microparticles showed good loading efficiency for all three drugs. DSC, SEM, XRD, and FTIR studies confirmed the entrapment of ivacaftor and ciprofloxacin. SEM and TEM scans observed the shape and the smooth surface. Antimicrobial synergism was proven by the agar broth, and dilution technique and the formulation was deemed safe by the results of the MTT assay.

Conclusion: Freeze-dried microparticles of ivacaftor, ciprofloxacin, and L-salbutamol could pave way to a hitherto unexplored combination of drugs as a novel approach to treat P. aeruginosa infcetions and bronchoconstriction commonly associated with cystic fibrosis.