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  • Title: One-step preparation of rifampicin/poly(lactic-co-glycolic acid) nanoparticle-containing mannitol microspheres using a four-fluid nozzle spray drier for inhalation therapy of tuberculosis.
    Author: Ohashi K, Kabasawa T, Ozeki T, Okada H.
    Journal: J Control Release; 2009 Apr 02; 135(1):19-24. PubMed ID: 19121349.
    Abstract:
    We prepared rifampicin (RFP)/poly(lactic-co-glycolic acid) (PLGA) nanoparticle-containing mannitol (MAN) microspheres for inhalation therapy of tuberculosis using a four-fluid nozzle spray drier in one step. The RFP and PLGA acetone/methanol (2/1) solution and MAN aqueous solution were supplied through different liquid passages of the four-fluid nozzle spray drier to obtain MAN microspheres including RFP/PLGA nanoparticles. The mean diameter of RFP/PLGA nanoparticles dispersed in MAN was 213 nm. The (RFP/PLGA)/MAN microspheres showed good in vitro aerosol performance evaluated using a cascade impactor. In an in vitro study of uptake by alveolar macrophage cells evaluated using coumarin 6 as a marker, the PLGA microparticles were more efficiently taken in than the PLGA nanoparticles. In an in vivo study of uptake of RFP by alveolar macrophages in the lungs of rats, the uptake of RFP from the RFP/PLGA microspheres was very small. The uptake of RFP from the (RFP/PLGA)/MAN microspheres, however, was larger, about 4%, at 1 h after administration increasing to 9.3% at 4 h. An in vivo imaging study suggests that the micron-sized PLGA particles were rapidly excreted from the lungs, but that it may be difficult to clear the nano-sized PLGA particles, resulting in their retention. Thus, the RFP/PLGA nanoparticles were recognized by alveolar macrophages and the uptake of RFP increased. This study shows that it is feasible to prepare RFP/PLGA nanoparticle-containing microspheres using a four-fluid nozzle spray drier in one step, and that the particles are retained in the lungs for prolonged periods and targeted to alveolar macrophages.
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