Freeze-dried vs spray-dried nanoplex DPIs based on chitosan and its derivatives conjugated with hyaluronic acid for tuberculosis: In vitro aerodynamic and in silico deposition profiles

Abstract

• Dry powder inhalers were developed for drug the delivery using nanotechnology. • Nanoparticles were synthesized using hyaluronic acid along with chitosan. • Also, hyaluronic acid was used with chitosan derivatives to prepare nanoparticles. • Spray-drying and freeze-drying were used as drying techniques to obtain nanopowders. • Stochastic lung model exhibited particle deposition in the lungs. • Drying techniques show small changes in sample profiles upon characterization. Dry powder inhalers (DPIs) are already on market, however, none of the DPIs are present for the treatment of tuberculosis. Herein, isoniazid-loaded nanopowders were developed for the delivery to the deeper lung tissues, more precisely alveoli. Chitosan (CS), thiolated chitosan (TC), and mannosylated chitosan (MC) were used individually in conjugation with hyaluronic acid (HA) because of their affinity for the pulmonary epithelium and alveolar macrophages. Here, the densities, Carr’s index, fine particle fraction (FPF), mass median aerodynamic diameter (MMAD), and in-silico behavior were examined by employing two drying techniques (freeze-drying and spray-drying) for nanopowders. During a preliminary evaluation, no significant difference was observed in the aerodynamic and in-silico profiles of the nanopowders produced by either drying technique. Nanopowders posed no toxicity to A549 cells as demonstrated by the MTT assay. Overall, the particle deposition profile was found to be promising for all the freeze-dried samples and spray-dried samples containing mannitol.