Formulation and Characterization of Nanocluster Ceftazidime for the Treatment of Acute Pulmonary Melioidosis
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Sara I Ruiz1, Nashwa El-Gendy2, Larry E Bowen3
1Aerobiology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702; Aerobiology, Ke'aki Technologies, Frederick, Maryland 21704.
Abstract:
Melioidosis is an infectious disease caused by Burkholderia pseudomallei. The disease is responsible for a high proportion of human pneumonia and fatal bacteremia in the endemic areas of the world and is highly resistant to most commonly available antibiotics. Studies have shown that prophylactic antibiotic treatment, when administered 24 h following bacterial challenge, can prevent infection in a murine model. Prophylactic treatment against this disease using a pulmonary antibiotic formulation has not previously been examined, but may reduce the number of treatments required, allow for the delivery of higher doses, eliminate the need for intravenous administration, and help to minimize systemic side effects. Ceftazidime was formulated as a dry powder aerosol suitable for pulmonary delivery using previously developed NanoCluster dry powder technology. Pharmacokinetics of aerosolized ceftazidime was analyzed in a mouse model. This study demonstrates that ceftazidime can be formulated using NanoCluster technology as a dry powder aerosol suitable for pulmonary delivery to humans. We have also demonstrated the retention of nebulized ceftazidime in mouse lungs for up to 6 h after exposure. The results indicate that this treatment may be useful as a prophylactic treatment against melioidosis. Future work will examine the efficacy of this treatment against B. pseudomallei aerosol challenge.
Insights
Pulmonary delivery of ceftazidime, an antibiotic, shows promise for preventing melioidosis. This novel formulation using NanoCluster technology may offer an effective prophylactic treatment against Burkholderia pseudomallei infections.
Area of Science:
- Infectious Diseases
- Pharmacology
- Pulmonary Drug Delivery
Background:
- Melioidosis, caused by Burkholderia pseudomallei, is a significant cause of pneumonia and fatal bacteremia in endemic regions.
- The disease exhibits high resistance to common antibiotics, necessitating alternative treatment strategies.
- Previous studies suggest prophylactic antibiotic treatment can prevent infection in murine models.
Purpose of the Study:
- To develop and evaluate a pulmonary antibiotic formulation for prophylactic melioidosis treatment.
- To investigate the feasibility of using NanoCluster dry powder technology for aerosolized ceftazidime delivery.
- To assess the pharmacokinetic profile and lung retention of aerosolized ceftazidime in a mouse model.
Main Methods:
- Ceftazidime was formulated as a dry powder aerosol using NanoCluster technology.
- Pharmacokinetics of aerosolized ceftazidime were analyzed in a mouse model.
- Lung retention of nebulized ceftazidime was measured up to 6 hours post-exposure.
Main Results:
- Successful formulation of ceftazidime as a dry powder aerosol suitable for pulmonary delivery.
- Demonstrated retention of aerosolized ceftazidime in mouse lungs for up to 6 hours.
- Established pharmacokinetic data for pulmonary delivered ceftazidime.
Conclusions:
- Aerosolized ceftazidime formulated via NanoCluster technology is suitable for pulmonary delivery.
- This formulation shows potential as a prophylactic treatment against melioidosis.
- Further studies are warranted to evaluate efficacy against Burkholderia pseudomallei aerosol challenge.
