Qin Xichun, Zhou Yeqing, Wang Yuzhuo, Wang Ziyao, Wang Yun, Chen Jiali, Zhu Lidong, Quan Xiaoyu, Liu Zhiwei, Zhang Hao, Jiang Liqun, Dong Hongyan, Zhang Zhongming
Department of Thoracic Cardiovascular Surgery, Affiliated Hospital of Xuzhou Medical University, China.
Jiangsu Key laboratory of New Drug research and clinical Pharmacy, Xuzhou Medical University, China.
Eur J Pharm Sci. 2021 Mar 1;158:105690. doi: 10.1016/j.ejps.2020.105690. Epub 2020 Dec 24.
In the treatment of heart disease, strategies for the targeted delivery of protein therapeutics to the heart by inhalation are still immature. Perfluorocarbons (PFCs) are inert chemicals with good biocompatibility, and unique physico-chemical properties that have recently led to their applications in numerous fields. In this study, we combined the advantages of protein-phospholipid complexes and PFC emulsions and then synthesized protein-loaded PFC nanoemulsions (PNEs) to test whether, after inhalation, these nanoemulsions could deliver therapeutic proteins to the heart. After preparing protein-phospholipid complexes by lyophilization, we obtained PNEs by extrusion. The particle size and surface charge of PNEs were about 140 nm and -50 mV, respectively. In vitro results showed that the PNEs had a fine particle fraction of 35% and exhibited sustained protein release. Translocation studies were done using three types of pulmonary epithelial cells, and ~7% translocation was observed in the Calu-3 cell line. Further, they were easily absorbed by cells and had therapeutic effects in culture. In vivo results showed that the PNEs successfully delivered proteins to the myocardial tissue of rats and reduced ischemic myocardial injury caused by acute myocardial infarction (AMI). This study suggests that inhalation of PNEs is a new potential strategy to deliver proteins to cardiac tissues for treating heart diseases.
在心脏病治疗中，通过吸入将蛋白质治疗药物靶向递送至心脏的策略仍不成熟。全氟化碳（PFCs）是具有良好生物相容性的惰性化学物质，其独特的物理化学性质使其最近在众多领域得到应用。在本研究中，我们结合了蛋白质 - 磷脂复合物和PFC乳液的优点，然后合成了载蛋白的PFC纳米乳液（PNEs），以测试这些纳米乳液在吸入后是否能够将治疗性蛋白质递送至心脏。通过冻干制备蛋白质 - 磷脂复合物后，我们通过挤压获得了PNEs。PNEs的粒径和表面电荷分别约为140 nm和 -50 mV。体外结果表明，PNEs的细颗粒分数为35%，并表现出蛋白质的持续释放。使用三种类型的肺上皮细胞进行转运研究，在Calu-3细胞系中观察到约7%的转运。此外，它们易于被细胞吸收并在培养中具有治疗作用。体内结果表明，PNEs成功地将蛋白质递送至大鼠心肌组织，并减轻了急性心肌梗死（AMI）引起的缺血性心肌损伤。本研究表明，吸入PNEs是一种将蛋白质递送至心脏组织以治疗心脏病的新的潜在策略。
