Dry powder formulation of kanamycin with enhanced aerosolization efficiency for drug-resistant tuberculosis

Area of Science:

• Pharmaceutical Sciences
• Drug Delivery Systems
• Pulmonary Medicine

Background:

• Kanamycin is used for drug-resistant tuberculosis (TB) but causes systemic toxicity via injection.
• Direct lung delivery of kanamycin could bypass systemic toxicity.
• This study aimed to create an aerosolizable kanamycin dry powder using l-leucine.

Purpose of the Study:

• To formulate a highly aerosolizable dry powder of kanamycin using spray-drying with l-leucine.
• To characterize the physicochemical properties and aerosolization performance of the formulated powders.
• To assess the stability and cytotoxicity of the kanamycin-l-leucine powders.

Main Methods:

• Kanamycin powders with varying l-leucine concentrations (0-20%) were prepared via spray-drying.
• Characterization included aerosolization efficiency (NGI), particle size (laser diffraction), morphology (SEM), crystallinity (X-ray), surface composition (XPS, ATR-FTIR), and moisture content (TGA).
• Stability was assessed after storage, and cytotoxicity was evaluated on Calu-3 and A549 cells (MTT assay).

Main Results:

• Spray-dried particles were within the inhalable size range (<6.1μm).
• Powders with l-leucine were amorphous, wrinkled, and had low moisture content (<5.0%).
• Kanamycin with 5% l-leucine achieved the highest aerosolization efficiency (73.0±2.5%) and remained stable during storage.

Conclusions:

• l-leucine enhances kanamycin aerosolization through surface modification.
• This approach offers a promising strategy for effective drug-resistant tuberculosis treatment via inhalation.
• The developed kanamycin dry powder is stable and well-tolerated by respiratory cell lines.