Nanoparticle-containing Microspheres Drug Delivery System (DDS) for Inhalation Therapy

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  • OZEKI Tetsuya
    Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Science
  • OKADA Hiroaki
    Laboratory of Pharmaceutics and Drug Delivery, Department of Pharmaceutical Science, School of Pharmacy, Tokyo University of Pharmacy and Life Science

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Other Title
  • ナノ薬物粒子含有マイクロスフェアによる経肺投与DDS
  • ナノ ヤクブツ リュウシ ガンユウ マイクロスフェア ニ ヨル ケイ ハイ トウヨ DDS

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Abstract

We have developed a new technology to prepare nanoparticle-containing composite microspheres using a 4-fluid nozzle spray drier in single step. An ethanol/sodium carbonate solution of pranlukast hydrate (PLH) and an aqueous solution of mannitol (MAN) were simultaneously supplied through different liquid channels of a 4-fluid nozzle spray drier (Fujisaki Electric, Tokushima, Japan) and then spray-dried to obtain composite microspheres containing PLH nanoparticles with PLH/MAN ratios of 1:4, and 1:10. Rifampicin (RFP) -MAN microspheres were also prepared in a manner similar to PLH. In vitro aerosol properties of the PLH powder and PLH-MAN and RFP-MAN composite microspheres were evaluated using a cascade impactor. The PLH-MAN composite microspheres with the PLH/MAN ratios of 1:4 and 1:10 were also administrated intratracheally to Sprague Dawley male rats. The residual percent of RFP in lung tissue was studied.<BR>The PLH/MAN microspheres were approximately 3μm in diameter and the PLH nanoparticles with diameters of 200-600nm could be prepared in the microspheres. However, the diameter of PLH nanoparticles varied with the PLH/MAN ratio. The pulmonary absorption was markedly higher for the PLH-MAN composite microspheres (100-fold increase in the AUC/dose) compared to the oral administration of PLH powder. The residual percentage of RFP in the lung with the intratracheal administration was significantly higher than that with the oral or intravenous administration during the initial stage, but RFP rapidly disappeared from the lung tissue and could not be observed four hours after the administration. Plasma concentration also rapidly decreased. Particulate design of RFP remaining in the lung and targeting the alveolar macrophage is required for more effective inhalation therapy of tuberculosis.

Journal

  • Earozoru Kenkyu

    Earozoru Kenkyu 21 (1), 10-15, 2006

    Japan Association of Aerosol Science and Technology

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