Nanoparticle-Based Dry Powder Inhaler Containing Ciprofloxacin for Enhanced Targeted Antibacterial Therapy

<b>Background</b>: Ciprofloxacin (CIP) is a poorly water-soluble fluoroquinolone-type antibiotic that can be useful in the treatment of lung infections. When the drugs are delivered directly to the lungs, a smaller dosage is needed to achieve the desired effect compared to the oral administration. Moreover, the application of nanoparticles potentially enhances the effectiveness of the treatments while lowering the possible side effects. Therefore, we aimed to develop a "nano-in-micro" structured dry powder inhaler formulation containing CIP. <b>Methods</b>: A two-step preparation method was used. Firstly, a nanosuspension was first prepared using a high-performance planetary mill by wet milling. After the addition of different additives (leucine and mannitol), the solid formulations were created by spray drying. The prepared DPI samples were analyzed by using laser diffraction, nanoparticle tracking analysis, scanning electron microscopy, X-ray powder diffraction, and differential scanning calorimetry. The solubility and in vitro dissolution tests in artificial lung fluid and in vitro aerodynamic investigations (Spraytec^® device, Andersen Cascade Impactor) were carried out. <b>Results</b>: The nanosuspension (D50: 140.0 ± 12.8 nm) was successfully prepared by the particle size reduction method. The DPIs were suitable for inhalation based on the particle diameter and their spherical shape. Improved surface area and amorphization after the preparation processes led to faster drug release. The excipient-containing systems were characterized by large lung deposition (fine particle fraction around 40%) and suitable aerodynamic diameter (between 3 and 4 µm). <b>Conclusions</b>: We have successfully formulated a nanosized antibiotic-containing formulation for pulmonary delivery, which could provide a potential treatment for patients with different respiratory infections.