Food and Drug Department, University of Parma, Parco Area delle Scienze 27/A, Parma 43124, Italy.
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 27/A, Parma 43124, Italy.
Eur J Pharm Sci. 2023 Dec 1;191:106609. doi: 10.1016/j.ejps.2023.106609. Epub 2023 Oct 13.
One of the strategies proposed for the neutralization of SARS-CoV-2 has been to synthetize small proteins able to act as a decoy towards the virus spike protein, preventing it from entering the host cells. In this work, the incorporation of one of these proteins, LCB1, within a spray-dried formulation for inhalation was investigated. A design of experiments approach was applied to investigate the optimal condition for the manufacturing of an inhalable powder. The lead formulation, containing 6% w/w of LCB1 as well as trehalose and L-leucine as excipients, preserved the physical stability of the protein and its ability to neutralize the virus. In addition, the powder had a fine particle fraction of 58.6% and a very high extra-fine particle fraction (31.3%) which could allow a peripheral deposition in the lung. The in vivo administration of the LCB1 inhalation powder showed no significant difference in the pharmacokinetic from the liquid formulation, indicating the rapid dissolution of the microparticles and the protein capability to translocate into the plasma. Moreover, LCB1 in plasma samples still maintained the ability to neutralize the virus. In conclusion, the optimized spray drying conditions allowed to obtain an inhalation powder able to preserve the protein biological activity, rendering it suitable for a systemic prevention of the viral infection via pulmonary administration.
一种针对 SARS-CoV-2 的中和策略是合成能够作为病毒刺突蛋白诱饵的小蛋白，从而阻止其进入宿主细胞。在这项工作中，研究了将其中一种蛋白质 LCB1 掺入喷雾干燥制剂中用于吸入的情况。应用实验设计方法来研究制造可吸入粉末的最佳条件。含 6%w/w LCB1 以及海藻糖和 L-亮氨酸作为赋形剂的主导配方保持了蛋白质的物理稳定性及其中和病毒的能力。此外，该粉末的微细颗粒分数为 58.6%，超细颗粒分数（31.3%）非常高，这可能允许在肺部进行周边沉积。LCB1 吸入粉末的体内给药在药代动力学方面与液体配方没有显著差异，表明微颗粒迅速溶解，蛋白质能够转移到血浆中。此外，血浆样品中的 LCB1 仍保持中和病毒的能力。总之，优化的喷雾干燥条件允许获得一种能够保持蛋白质生物活性的吸入粉末，使其适合通过肺部给药进行病毒感染的全身预防。
