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

Area of Science:

• Pharmaceutical Sciences
• Nanotechnology
• Pulmonary Drug Delivery

Background:

• Ethambutol hydrochloride (EMB) is a key anti-tuberculosis drug.
• Oral administration of EMB is associated with side effects and cellular toxicity.
• Pulmonary drug delivery presents an alternative to overcome oral administration limitations.

Purpose of the Study:

• To develop and evaluate ethambutol hydrochloride-loaded solid lipid nanoparticles (SLNs) for pulmonary administration via a dry powder inhaler (DPI).
• To assess the feasibility of direct lung delivery of EMB to mitigate systemic toxicity and improve therapeutic outcomes for tuberculosis.

Main Methods:

• EMB-loaded SLNs were prepared using hot homogenization and ultrasonication techniques.
• DPI formulations were created by spray drying EMB-loaded SLNs with and without mannitol.
• Powder flowability was assessed using Carr's index and Hausner ratio; in vitro deposition was evaluated using the Next Generation Impactor (NGI).

Main Results:

• High encapsulation efficiency (>98%) and sub-100 nm particle size were achieved for EMB-loaded SLNs.
• MTT assay confirmed the biocompatibility and non-toxicity of the SLNs.
• Flowability and aerodynamic assessments indicated the suitability of the EMB-loaded SLN DPI powder for pulmonary delivery.

Conclusions:

• EMB-loaded SLN DPI formulations demonstrate excellent characteristics for direct pulmonary delivery.
• This novel approach holds significant potential for the effective treatment of tuberculosis with reduced systemic side effects.
• Pulmonary administration of EMB via SLN-based DPI represents a promising strategy for tuberculosis management.