Department of Chemical Engineering, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel.
Division of Neonatology and Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Int J Pharm. 2020 Jul 30;585:119387. doi: 10.1016/j.ijpharm.2020.119387. Epub 2020 May 27.
Preterm infants, particularly those who born between 23 and 28 weeks' gestation, suffer from a very high incidence of respiratory distress syndrome (RDS) related to pulmonary immaturity and inability to make Pulmonary Surfactant (PS). These infants are supported by the use of oxygen, ventilators, and routine administration of surfactant replacement. The currently commercial surfactant replacement therapies do not contain hydrophilic surfactant proteins such as Surfactant Protein D (SP-D). These proteins have a key role in the innate lung host defense, thus the development of a sustained release vehicle that provides SP-D for long periods in preterm infants' lungs would exploit the therapeutic potential of SP-D and other pulmonary medications. The proposed SP-D delivery system is based on nanoparticles (NPs) composed of poly (lactic acid-co-glycolic acid) (PLGA), a biodegradable, FDA approved biopolymer. The resulted NPs were spherical with high Zeta potential value, were not toxic to A-549 lungs cells, and did not induce any inflammatory response in mouse's lungs for short and long-term periods. Moreover, SP-D released from NPs showed biological activity for several days and in vivo release experiment of SP-D loaded NPs revealed that SP-D was released from NPs in mouse lungs with different NPs delivery doses.
早产儿,尤其是那些在 23 周到 28 周之间出生的早产儿,患有很高的呼吸窘迫综合征(RDS)的发病率,这与肺部不成熟和无法产生肺表面活性剂(PS)有关。这些婴儿通过使用氧气、呼吸机和常规的表面活性剂替代物来支持。目前的商业表面活性剂替代疗法不包含亲水表面活性剂蛋白,如表面活性剂蛋白 D(SP-D)。这些蛋白质在先天肺宿主防御中起着关键作用,因此开发一种能够在早产儿肺部中长时间提供 SP-D 的缓释载体将利用 SP-D 和其他肺部药物的治疗潜力。拟议的 SP-D 传递系统基于由聚(乳酸-co-乙醇酸)(PLGA)组成的纳米颗粒(NPs),PLGA 是一种可生物降解的、FDA 批准的生物聚合物。得到的 NPs 呈球形,具有高 Zeta 电位值,对 A-549 肺细胞没有毒性,并且在短期和长期内不会在小鼠肺部引起任何炎症反应。此外,从 NPs 中释放的 SP-D 表现出数天的生物活性,并且体内释放实验表明,不同 NPs 给药剂量的 SP-D 从 NPs 中在小鼠肺部释放。