Ethambutol-Loaded Solid Lipid Nanoparticles as Dry Powder Inhalable Formulation for Tuberculosis Therapy

Ethambutol hydrocloride (EMB) is an anti-tuberculosis drug, which is commonly used as a protection agent against of unrecognized resistance to other drugs employed to treat this disease. Since oral form of EMB has some side effects and cellular toxicity, direct administration of EMB into lungs seems to be an attractive and reasonable option in order to overcome these side effects. Our main goal in this study was assessment of pulmonary administration through dry powder inhaler (DPI) using EMB-loaded solid lipid nanoparticles (SLNs). We prepared EMB-loaded SLNs using two techniques (hot homogenization and ultrasonication). DPI formulations were made by spray drying of EMB-loaded SLNs with and without mannitol. For investigation of flowbility of the prepared powders, Carr's index and Hausner ratio, and for in vitro deposition of the powders, Next Generation Impactor (NGI) analysis were used. The encapsulation efficiency and particle size of obtained particles were higher than 98% and sub-100 nm, respectively. Toxicity investigation of EMB-loaded SLNs via MTT assay showed biocompatibility and non-toxicity of the SLNs. Results of flowability and aerodynamic traits assessment of EMB-loaded SLN DPI powder confirmed the suitability of prepared powders. Overall, the attained results showed that EMB-loaded SLN DPI has high potential for direct treatment of tuberculosis.