Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, 6B, Shixun Building, 1239 Siping Road, Yangpu District, 20092 China.
College of Animal Sciences and Technology, Guangxi University, Nanning, 530004, China.
Biol Open. 2020 Jun 14;9(6):bio052241. doi: 10.1242/bio.052241.
Large-scale compound screening in adult flies is hampered by the lack of continuous drug delivery systems and poor solubility of numerous compounds. Here we found that gum Arabic (Acacia/Senegal gum), a widely used stabilizer, can also emulsify lipophilic compounds and profoundly increase their accessibility to target tissues in and mice. We further developed a gum Arabic-based drug delivery system, wherein the drug was ground into gum Arabic and emulsified in liquid food fed to flies by siphoning through a U-shape glass capillary. This system did not affect food intake nor cell viability. Since drugs were continuously delivered by siphoning, minimal compound waste and less frequent food changes make this system ideal for large-scale long-term screenings. In our pilot screening for antitumor drugs in the NCI DTP library, we used a model of colorectal cancer and identified two drugs that are especially hydrophobic and were not identified in previous screenings. Our data demonstrated that gum Arabic facilitates drug delivery in animal models and the system is suitable for long-term high-throughput drug screening in This system would accelerate drug discovery for chronic and cognitive conditions.
大规模的成年果蝇化合物筛选受到缺乏连续药物输送系统和许多化合物溶解度差的阻碍。在这里，我们发现阿拉伯树胶（Acacia/Senegal 树胶），一种广泛使用的稳定剂，也可以乳化亲脂性化合物，并显著增加它们在和小鼠中的靶组织的可及性。我们进一步开发了一种基于阿拉伯树胶的药物输送系统，其中药物被磨成阿拉伯树胶并在液体食物中乳化，通过虹吸通过 U 形玻璃毛细管输送给苍蝇。该系统不影响食物摄入也不影响细胞活力。由于虹吸输送持续提供药物，因此最小化了化合物浪费和减少了频繁更换食物，使该系统成为大规模长期筛选的理想选择。在我们对 NCI DTP 文库中的抗肿瘤药物的初步筛选中，我们使用了结直肠癌的模型，并鉴定出两种特别疏水的药物，这些药物在以前的筛选中没有被鉴定出来。我们的数据表明，阿拉伯树胶有助于在动物模型中输送药物，并且该系统适合于在长期高通量药物筛选。该系统将加速治疗慢性和认知疾病的药物发现。
