Department of Pediatrics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
Sci Rep. 2021 Aug 12;11(1):16439. doi: 10.1038/s41598-021-95999-0.
Inhalation of dry powder synthetic lung surfactant may assist spontaneous breathing by providing noninvasive surfactant therapy for premature infants supported with nasal continuous positive airway pressure. Surfactant was formulated using spray-drying with different phospholipid compositions (70 or 80 total weight% and 7:3 or 4:1 DPPC:POPG ratios), a surfactant protein B peptide analog (KL4, Super Mini-B, or B-YL), and Lactose or Trehalose as excipient. KL4 surfactant underperformed on initial adsorption and surface activity at captive bubble surfactometry. Spray-drying had no effect on the chemical composition of Super Mini-B and B-YL peptides and surfactant with these peptides had excellent surface activity with particle sizes and fine particle fractions that were well within the margins for respiratory particles and similar solid-state properties. Prolonged exposure of the dry powder surfactants with lactose as excipient to 40 °C and 75% humidity negatively affected hysteresis during dynamic cycling in the captive bubble surfactometer. Dry powder synthetic lung surfactants with 70% phospholipids (DPPC and POPG at a 7:3 ratio), 25% trehalose and 3% of SMB or B-YL showed excellent surface activity and good short-term stability, thereby qualifying them for potential clinical use in premature infants.
干粉合成肺表面活性剂的吸入可以通过为接受鼻持续气道正压通气支持的早产儿提供非侵入性表面活性剂治疗来辅助自主呼吸。表面活性剂的配方采用喷雾干燥法,使用不同的磷脂成分(总重量的 70%或 80%,DPPC:POPG 比例为 7:3 或 4:1)、表面活性蛋白 B 肽类似物(KL4、Super Mini-B 或 B-YL)以及乳糖或海藻糖作为赋形剂。KL4 表面活性剂在封闭气泡表面张力仪中的初始吸附和表面活性方面表现不佳。喷雾干燥对 Super Mini-B 和 B-YL 肽的化学成分没有影响,并且这些肽的表面活性剂具有极好的表面活性,颗粒大小和细微颗粒分数都在呼吸颗粒的范围内,并且具有相似的固态特性。乳糖作为赋形剂的干粉表面活性剂在 40°C 和 75%湿度下长时间暴露会对封闭气泡表面张力仪中的动态循环过程中的滞后产生负面影响。含有 70%磷脂(DPPC 和 POPG 比例为 7:3)、25%海藻糖和 3%SMB 或 B-YL 的 70%干粉合成肺表面活性剂具有极好的表面活性和良好的短期稳定性,因此有资格在早产儿中进行潜在的临床应用。