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Published on: August 18, 2023
Spray-Dried Inhalable Powder Formulations of Gentamicin Designed for Pneumonic Plague Therapy in a Mouse Model
Menghuan Zhu1,2, Dongna Zhang2, Lili Zhang2
1School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, China.
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.
Insights
Inhaling gentamicin (GM) dry powders, created via spray-drying, offers an effective, noninvasive treatment for pneumonic plague. This pulmonary drug delivery method targets infection locally, reducing systemic toxicity risks associated with traditional plague treatments.
Area of Science:
- Pharmacology
- Drug Delivery
- Infectious Diseases
Background:
- Pneumonic plague, caused by Yersinia pestis, is fatal without prompt treatment.
- Current treatments like gentamicin (GM) require invasive administration (intramuscular or intravenous).
- Pulmonary drug delivery presents a noninvasive alternative with targeted local action and reduced systemic toxicity.
Purpose of the Study:
- To develop and optimize spray-dried gentamicin powders for pulmonary inhalation.
- To evaluate the efficacy of inhaled gentamicin for treating pneumonic plague.
Main Methods:
- Gentamicin powders were prepared using spray-drying technology.
- A 3^2 full factorial design optimized formulation (15% L-leucine) and process parameters (120°C inlet temperature, 15% pump rate).
- Powder characteristics (morphology, crystallinity, fluidity, particle size) and therapeutic efficacy in a mouse pneumonic plague model were assessed.
Main Results:
- Optimized spray-dried GM powders exhibited favorable physical and chemical properties suitable for inhalation.
- Inhalation therapy demonstrated significant therapeutic effects in a mouse model of pneumonic plague.
- Comparison showed dry powder atomization to be an effective administration route.
Conclusions:
- Spray-dried gentamicin powders are a viable option for pulmonary drug delivery.
- Inhalation therapy with GM spray-dried powders presents an effective treatment strategy for pneumonic plague.
- This approach offers a noninvasive alternative to conventional administration routes.
