Spray-Dried Inhalable Powder Formulations of Gentamicin Designed for Pneumonic Plague Therapy in a Mouse Model

Abstract

Infection with Yersinia pestis (Y. pestis) may cause pneumonic plague, which is inevitably fatal without treatment. Gentamicin (GM), an aminoglycoside antibiotic, is a drug commonly used in the treatment of plague. However, it requires repeated intramuscular or intravenous administration. Pulmonary drug delivery is noninvasive, with the advantages of local targeting and reduced risk of systemic toxicity. In this study, GM powders were prepared using spray-drying technology. The powders displayed good physical and chemical properties and met the requirements for human pulmonary inhalation. The formulation of the powders was optimized using a 32 full factorial design. A formulation of 15% (w/w) of L-leucine was prepared, and the spray-drying process parameters using an inlet temperature of 120°C and a 15% pump rate were determined to produce the best powder. In addition, the optimized GM spray-dried powders were characterized in terms of morphology, crystallinity, powder fluidity, and aerodynamic particle size distribution analysis. In a mouse model of pneumonic plague, we compared the therapeutic effects among three administration routes, including subcutaneous injection, liquid atomization, and dry powder atomization. In conclusion, our data suggest that inhalation therapy with GM spray-dried powders is an effective treatment for pneumonic plague.

Development of Large Hollow Particles for Pulmonary Delivery of Cyclosporine A

“…Raw CsA and HPMC had no representative crystal peaks but two broad peaks, indicating that raw CsA and HPMC had an amorphous structure [ 46 , 47 ]. The LEU had characteristic peaks with high intensities at 6.1°, 12.1°, 24.4°, 30.6°, and 36.9°, indicating that LEU had a crystalline structure [ 48 , 49 ]. The characteristic peaks of LEU could be observed on the spectra of CsA-LEU and CsA-LEU-0.8HPMC-AB with a much lower intensity, indicating that CsA-LEU and CsA-LEU-0.8HPMC-AB exhibited a low-crystalline structure after spray drying.…”