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    首頁> 外文學位 >Pulmonary delivery of isoxyl particles to treat Mycobacterium tuberculosis.
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    Pulmonary delivery of isoxyl particles to treat Mycobacterium tuberculosis.

    機譯:異氧基顆粒的肺部輸送以治療結核分枝桿菌。

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    摘要

    Isoxyl is an effective drug to treat multi-drug resistant tuberculosis but its use was impaired by failure in clinical trials. Due to absence of reliable quantitive analytical methods at that time, the reasons for these poor in-vivo outcomes were not determined. In the present work, an HPLC method was developed and validated for determination of isoxyl concentrations in plasma. Pilot studies showed that therapeutic plasma concentrations were not achieved after oral administration of isoxyl to guinea pigs. Pulmonary delivery may rescue the drug by targeting isoxyl particles to macrophages, the host cells of mycobacteria. Isoxyl particles with various size and shape were prepared by antisolvent precipitation. Subsequent spray drying produced microparticles 5 mum suitable for lung delivery. Isoxyl ≥ 5 mug/ml, independent of particle form, seemed effective in killing intracellular mycobacteria without cytotoxicity. This work is the basis for reviving drugs with undesired physicochemical properties to treat lung infection.
    機譯:異羥是治療多藥耐藥結核病的有效藥物,但由于臨床試驗失敗,其使用受到了影響。由于當時缺乏可靠的定量分析方法,因此尚無法確定這些不良體內結果的原因。在目前的工作中,開發了一種HPLC方法并驗證了該方法可用于測定血漿中的異氧基濃度。試點研究表明,對豚鼠口服異氧基后,未達到治療性血漿濃度。肺部遞送可通過將異氧基顆粒靶向分枝桿菌的宿主細胞巨噬細胞來拯救藥物。通過反溶劑沉淀制備具有各種尺寸和形狀的異氧基顆粒。隨后的噴霧干燥產生了小于5微米的微粒,適合于肺部輸送。異氧基≥5杯/毫升,獨立于顆粒形式,似乎可以有效殺死細胞內分枝桿菌而無細胞毒性。這項工作是復活具有不良理化特性的藥物以治療肺部感染的基礎。

    著錄項

    • 作者

      Wang, Chenchen.;

    • 作者單位

      The University of North Carolina at Chapel Hill.;

    • 授予單位 The University of North Carolina at Chapel Hill.;
    • 學科 Chemistry Pharmaceutical.
    • 學位 M.S.
    • 年度 2010
    • 頁碼 114 p.
    • 總頁數 114
    • 原文格式 PDF
    • 正文語種 eng
    • 中圖分類
    • 關鍵詞

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