Lipid microsphere formulation containing rifampicin targets alveolar macrophages.
The study demonstrated that lipid microspheres (LM) containing rifampicin (LM-RFP) could deliver the drug to alveolar macrophages in vitro and in vivo, and that intranasal administration to animals could achieve preferential accumulation in the lungs with less effect on the liver. The LM-RFP particles had a mean diameter of 247.2 +/- 75.7 nm, and their size remained stable when stored at 4 degrees C or 25 degrees C for at least 4 weeks. In vitro uptake of [(3)H]LM-RFP by alveolar macrophages was over 4 times higher than that of unencapsulated [(3)H]RFP, whereas the in vivo uptake was 30 times higher. Flow cytometric analysis and confocal laser scanning microscopy confirmed that LM could deliver the encapsulated drug effectively to alveolar macrophages in vitro and in vivo. Intranasal administration of [(3)H]LM-RFP to normal mice resulted in preferential pulmonary uptake of the drug and lower levels in the blood and liver compared with administration of unencapsulated [(3)H]RFP. In conclusion, LM-RFP could be a promising preparation for delivery via the respiratory tract to tuberculosis (TB) and TB/HIV patients.
Takenaga
M
M
Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki, Japan. m2take@marianna-u.ac.jp
Ohta
Y
Y
Tokura
Y
Y
Hamaguchi
A
A
Igarashi
R
R
Disratthakit
A
A
Doi
N
N
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002460:Cell Line; D016503:Drug Delivery Systems / Q000379:methods; D007278:Injections, Spinal; D007668:Kidney / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008863:Microspheres; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012293:Rifampin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution; D014316:Tritium
D008055:Lipids; D014316:Tritium; D012293:Rifampin