A hand-held apparatus for "nose-only" exposure of mice to inhalable microparticles as a dry powder inhalation targeting lung and airway macrophages.
Microparticles containing isoniazid and rifabutin were aerosolised using a simple apparatus fabricated from a 15-ml centrifuge tube. The dose available for inhalation by rodents was determined by collecting microparticles emitted at the delivery port. The dose available for inhalation was proportional to durations of exposure ranging from 10 to 90 s (10.5-13.5 CV%) and the weight of powder taken for fluidization (10-50 mg, r2=0.982). The apparatus was then used to administer inhalations of microparticles to mice. Other groups of mice received free rifabutin orally, or by i.v. injection. Rifabutin was estimated in serum and tissues of dosed mice by HPLC. When approximately 20 mg of microparticles were loaded in the apparatus, approximately 2.5 mg were collected at the delivery port in 30 s of operation. Mice inhaled approximately 300 microg of the 2.5 mg emitted at the delivery port. Airway and lung macrophages of mice receiving inhalations for 30 s accumulated 0.38 microg of rifabutin, while the amount in blood serum of these mice was 0.62 microg. In mice receiving 83 microg rifabutin i.v. or orally, the intracellular amounts were 0.06 and 0.07 microg respectively, while the amounts in serum were 1.02 and 0.80 microg. These observations confirmed that inhalation of microparticles targeted airway and lung macrophages.
Kaur
Jatinder
J
Pharmaceutics Division, Central Drug Research Institute, Lucknow 226001, India.
Muttil
Pavan
P
Verma
Rahul Kumar
RK
Kumar
Kaushlendra
K
Yadav
Awadh Bihari
AB
Sharma
Rolee
R
Misra
Amit
A
D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D001239:Inhalation; D007275:Injections, Intravenous; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D011208:Powders; D012137:Respiratory System / Q000166:cytology / Q000378:metabolism*; D017828:Rifabutin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D018675:Toxicity Tests / Q000295:instrumentation*
D000995:Antitubercular Agents; D011208:Powders; D017828:Rifabutin