Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy , The University of Texas at Austin , 2409 University Avenue , Austin , Texas 78712 , United States.
Lung Therapeutics Inc. , 2600 Via Fortuna, Suite 360 , Austin , Texas 78746 , United States.
Mol Pharm. 2020 Feb 3;17(2):632-644. doi: 10.1021/acs.molpharmaceut.9b01085. Epub 2020 Jan 8.
The caveolin scaffolding domain peptide (CSP) is being developed for the therapeutic intervention of a lethal lung disease, idiopathic pulmonary fibrosis. While direct respiratory delivery of CSP7 (a 7-mer fragment of CSP) is considered an effective route, proper formulation and processing of the peptide are required. First, air-jet milling technology was performed in order to micronize the neat peptide powder. Next, the fine particles were subjected to a stability study with physical and chemical characterizations. In addition, the efficacy of processed CSP7 powder was evaluated in an animal model of lung fibrosis. The results revealed that, with jet milling, the particle size of CSP7 was reduced to a mass median aerodynamic diameter of 1.58 ± 0.1 μm and 93.3 ± 3.3% fine particle fraction, optimal for deep lung delivery. A statistically significant reduction of collagen was observed in diseased lung tissues of mice that received CSP7 powder for inhalation. The particles remained chemically and physically stable after micronization and during storage. This work demonstrated that jet milling is effective in the manufacturing of a stable, excipient-free CSP7 inhalation powder for the treatment of pulmonary fibrosis.
窖蛋白 scaffolding 结构域肽（CSP）正在被开发用于治疗一种致命的肺部疾病，特发性肺纤维化。虽然直接呼吸给予 CSP7（CSP 的一个 7 个氨基酸的片段）被认为是一种有效的途径，但是需要对肽进行适当的配方和处理。首先，采用气流粉碎技术对纯肽粉末进行微米化处理。然后，对精细颗粒进行物理和化学特性的稳定性研究。此外，还在肺纤维化的动物模型中评估了加工后的 CSP7 粉末的功效。结果表明，采用喷气式研磨，CSP7 的粒径减小至质量中值空气动力学直径为 1.58±0.1μm，细颗粒分数为 93.3±3.3%，非常适合肺部深层给药。接受 CSP7 粉末吸入治疗的患病小鼠的肺部组织中胶原明显减少。颗粒在微米化后和储存期间保持化学和物理稳定性。这项工作表明，喷气式研磨在制造稳定、无赋形剂的 CSP7 吸入粉末用于治疗肺纤维化方面是有效的。
