J. Gabrielsson, D. Weiner. Pharmacokinetic, Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts & Applications, fourth ed. 1250 pp., figures and diagrams in colour, 2500, Price: 993 SEK +
- 作者：Harold Boxenbaum
- 关键词：Dry powder inhalation ; Respirable microspheres ; Targeting ; Macrophages ; Pulmonary delivery ; Tuberculosis
- 刊名：European Journal of Pharmaceutical Sciences
- 出版年：2007
- 期刊代码：15_09280987
- 类别：pha
- 出版时间：October 2007
- 卷：32
- 期：2
- 页码：151
- 文件大小：110 K
摘要
Microparticles containing large payloads of two anti-tuberculosis (TB) drugs were prepared and evaluated for suitability as a dry powder inhalation targeting alveolar macrophages. A solution containing one part each of isoniazid and rifabutin, plus two parts poly(lactic acid) (L-PLA) was spray-dried. Drug content and in vitro release were assayed by HPLC, and DSC was used to elucidate release behaviour. Particle size was measured by laser scattering and aerosol characteristics by cascade impaction using a Lovelace impactor. Microparticles were administered to mice using an in-house inhalation apparatus or by intra-tracheal instillation. Drugs in solution were administered orally and by intra-cardiac injection. Flow cytometry and HPLC were used to investigate the specificity and magnitude of targeting macrophages. Microparticles having drug content 
50%(w/w), particle size 5 μm and satisfactory aerosol characteristics (median mass aerodynamic diameter, MMAD = 3.57 μm; geometric standard deviation, GSD = 1.41 μm; fine particle fraction, FPF<4.6μm = 78.91 ± 8.4%) were obtained in yields of >60%. About 70%of the payload was released in vitro in 10 days. Microparticles targeted macrophages and not epithelial cells on inhalation. Drug concentrations in macrophages were 20 times higher when microparticles were inhaled rather than drug solutions administered. Microparticles were thus deemed suitable for enhanced targeted drug delivery to lung macrophages.
50%(w/w), particle size 5 μm and satisfactory aerosol characteristics (median mass aerodynamic diameter, MMAD = 3.57 μm; geometric standard deviation, GSD = 1.41 μm; fine particle fraction, FPF<4.6μm = 78.91 ± 8.4%) were obtained in yields of >60%. About 70%of the payload was released in vitro in 10 days. Microparticles targeted macrophages and not epithelial cells on inhalation. Drug concentrations in macrophages were 20 times higher when microparticles were inhaled rather than drug solutions administered. Microparticles were thus deemed suitable for enhanced targeted drug delivery to lung macrophages.