title: Formulation and Characterization of Nanocluster Ceftazidime for the Treatment of Acute Pulmonary Melioidosis.
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.
authors.affiliation: Aerobiology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702; Aerobiology, Ke'aki Technologies, Frederick, Maryland 21704.
authors.forename: Sara I
authors.initials: SI
authors.lastname: Ruiz
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047.
authors.forename: Nashwa
authors.initials: N
authors.lastname: El-Gendy
authors.affiliation: Aerobiology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702; Aerobiology, Ke'aki Technologies, Frederick, Maryland 21704; Aerobiology, Clinical Research Management, Frederick, Maryland 21701.
authors.forename: Larry E
authors.initials: LE
authors.lastname: Bowen
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047; Department of Chemical & Petroleum Engineering, The University of Kansas, Lawrence, Kansas 66045.
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
authors.affiliation: Aerobiology, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland 21702. Electronic address: mark.m.bailey2.mil@mail.mil.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Bailey
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D016957:Burkholderia pseudomallei / Q000187:drug effects; D002442:Ceftazidime / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D004339:Drug Compounding; D005260:Female; D008554:Melioidosis / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D012141:Respiratory Tract Infections / Q000188:drug therapy* / Q000378:metabolism; D016896:Treatment Outcome; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D002442:Ceftazidime
keywords: NanoCluster; aerosols; ceftazidime; dry powder; pulmonary melioidosis