9-Nitrocamptothecin liposome aerosol treatment of melanoma and osteosarcoma lung metastases in mice.
9-Nitrocamptothecin liposome aerosol treatment of melanoma and osteosarcoma lung metastases in mice.
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发表时间：
2000-07
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通讯作者：
N. Koshkina;E. Kleinerman;C. Waldrep;S. Jia;L. Worth;B. Gilbert;V. Knight
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作者：
N. Koshkina;E. Kleinerman;C. Waldrep;S. Jia;L. Worth;B. Gilbert;V. Knight
复发性骨肉瘤和黑色素瘤肺转移对传统静脉化疗方案的反应率令人失望。将化疗药物直接输送到肺部可以增加肿瘤区域的药物浓度，并可能为这些患者提供新的治疗方法。先前的研究表明，与肠胃外和口服给药相比，以脂质体制剂递送至呼吸道的药物导致高的肺部药物浓度、降低的全身毒性和降低的剂量要求。为了确定这种方法是否具有针对肺转移的效用，使用两种不同的实验肺转移模型来确定用脂质体包封的9-硝基喜树碱（L-9 NC）的气雾剂疗法的功效。在静脉内注射B16黑素瘤细胞后的第二天，用气溶胶L-9 NC（153微克9-硝基喜树碱/kg）处理C57 BL/6小鼠1小时，每周5天，最多3周。气溶胶L-9 NC治疗导致肺重量（P = 0.005）和肿瘤病灶数量（P < 0.001）减少。9-硝基喜树碱治疗组可见的肿瘤结节比未治疗的对照组少且小（P < 0.001）。使用新开发的人骨肉瘤裸鼠实验转移模型，我们证明了气雾剂L-9 NC对已建立的肺转移瘤也有效。在静脉注射肿瘤后第9周开始气雾剂治疗并持续8或10周，可显著减少具有可见和显微镜下病变的动物数量（P < 0.02）、肺中肿瘤病灶总数（P < 0.005）和单个肿瘤结节的大小（P < 0.02）。这些数据表明，L-9 NC气雾剂治疗黑色素瘤和骨肉瘤肺转移瘤可能提供显着的优势，在现有的方法。
The response rates of relapsed osteosarcoma and melanoma pulmonary metastases to traditional i.v. chemotherapeutic regimens have been disappointing. Direct drug delivery of chemotherapy to the lungs could increase the drug concentration in the tumor area and may offer a new therapeutic approach for these patients. Previous studies demonstrated that drugs delivered to the respiratory tract in liposomal formulation resulted in high pulmonary drug concentration, reduced systemic toxicity, and reduced dosage requirements compared with parenteral and oral administration. To determine whether this approach has utility against pulmonary metastases, the efficacy of aerosol therapy with liposome-encapsulated 9-nitrocamptothecin (L-9NC) was determined using two different experimental lung metastasis models. C57BL/6 mice were treated the day after the i.v. injection of B16 melanoma cells with aerosol L-9NC for 1 h (153 microg 9-nitrocamptothecin/kg) for 5 days per week for up to 3 weeks. Aerosol L-9NC treatment resulted in a reduction in lung weights (P = 0.005) and number of tumor foci (P < 0.001). Visible tumor nodules were fewer and smaller in the 9-nitrocamptothecin-treated group than in untreated control mice (P < 0.001). Using a newly developed human osteosarcoma experimental metastasis model in nude mice, we demonstrated that aerosol L-9NC was also effective against established lung metastases. Aerosol therapy initiated on the ninth week after i.v. tumor injection and continued for 8 or 10 weeks produced highly significant reductions in the number of animals with both visible and microscopic disease (P < 0.02), the total number of tumor foci in the lungs (P < 0.005), and the size of the individual tumor nodules (P < 0.02). These data suggest that L-9NC aerosol therapy may offer significant advantage over existing methods in the treatment of melanoma and osteosarcoma pulmonary metastases.