Excipient Enhanced Growth Aerosol Surfactant Replacement Therapy in an In Vivo Rat Lung Injury Model
Excipient Enhanced Growth Aerosol Surfactant Replacement Therapy in an In Vivo Rat Lung Injury Model
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DOI：
10.1089/jamp.2020.1593
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发表时间：
2020-05-21
影响因子：
3.4
通讯作者：
Heise, Rebecca L.
中科院分区：
文献类型：
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作者：
Gninzeko, Franck J. Kamga;Valentine, Michael S.;Heise, Rebecca L.
背景：在新生儿呼吸窘迫综合征中，呼吸支持和表面活性物质治疗通常用于使肺泡扩张。表面活性剂通常通过液体滴注递送。然而，液体滴注并不专门针对小气道。我们已经使用Survanta（R）开发了赋形剂增强生长（EEG）粉末气雾剂制剂。使用新型干粉吸入器通过气管吹入将EEG Survanta粉末气雾剂以标称剂量3、5、10和20 mg粉末（含有0.61、0.97、1.73和3.46 mg磷脂（PL））递送至表面活性剂耗尽的大鼠，而液体Survanta通过注射器滴注以2和4 mL/kg的剂量递送，含有18.6和34 mg PL。通气力学测量之前和之后耗尽，和治疗后。我们假设，EEG Survanta粉末气雾剂将改善肺力学与灌输液体Survanta在表面活性剂depletedrates.Results和结论：EEG Survanta粉末气雾剂在0.61毫克PL的剂量显着改善肺顺应性和弹性相比，液体Survanta在18.6毫克的剂量，这代表了改善的主要疗效的气雾剂在一个30倍低剂量的PL。EEG Survanta组灌洗液中的白色血细胞计数与液体Survanta组相比无显著差异。这些结果为EEG Survanta粉末气雾剂作为表面活性剂替代疗法的有前途的方法提供了体内概念验证。
Background: In neonatal respiratory distress syndrome, breathing support and surfactant therapy are commonly used to enable the alveoli to expand. Surfactants are typically delivered through liquid instillation. However, liquid instillation does not specifically target the small airways. We have developed an excipient enhanced growth (EEG) powder aerosol formulation using Survanta(R).Methods: EEG Survanta powder aerosol was delivered using a novel dry powder inhaler via tracheal insufflation to surfactant depleted rats at nominal doses of 3, 5, 10, and 20 mg of powder containing 0.61, 0.97, 1.73, and 3.46 mg of phospholipids (PL), whereas liquid Survanta was delivered via syringe instillation at doses of 2 and 4 mL/kg containing 18.6 and 34 mg of PL. Ventilation mechanics were measured before and after depletion, and after treatment. We hypothesized that EEG Survanta powder aerosol would improve lung mechanics compared with instilled liquid Survanta in surfactant depleted rats.Results and Conclusion: EEG Survanta powder aerosol at a dose of 0.61 mg PL significantly improved lung compliance and elastance compared with the liquid Survanta at a dose of 18.6 mg, which represents improved primary efficacy of the aerosol at a 30-fold lower dose of PL. There was no significant difference in white blood cell count of the lavage from the EEG Survanta group compared with liquid Survanta. These results provide an in vivo proof-of-concept for EEG Survanta powder aerosol as a promising method of surfactant replacement therapy.