Nicolas Alexandre, Dejoux Alice, Poirier Cécile, Aubrey Nicolas, Péan Jean-Manuel, Velge-Roussel Florence
GICC EA 7501, Faculty of Medicine, University of Tours, 37032 Tours, France.
PEX DPH, Technologie Servier, 45000 Orleans, France.
Pharmaceutics. 2020 Sep 26;12(10):921. doi: 10.3390/pharmaceutics12100921.
Single-domain antibodies (sdAbs) offer great features such as increased stability but are hampered by a limited serum half-life. Many strategies have been developed to improve the sdAb half-life, such as protein engineering and controlled release systems (CRS). In our study, we designed a new product that combined a hydrogel with a 3D-printed implant. The results demonstrate the implant's ability to sustain sdAb release up to 13 days through a reduced initial burst release followed by a continuous release. Furthermore, formulation screening helped to identify the best sdAb formulation conditions and improved our understanding of our CRS. Through the screening step, we gained knowledge about the influence of the choice of polymer and about potential interactions between the sdAb and the polymer. To conclude, this feasibility study confirmed the ability of our CRS to extend sdAb release and established the fundamental role of formulation screening for maximizing knowledge about our CRS.
单域抗体(sdAbs)具有诸多优点,如稳定性增强,但血清半衰期有限,这限制了其应用。人们已开发出多种策略来延长sdAbs的半衰期,例如蛋白质工程和控释系统(CRS)。在我们的研究中,我们设计了一种将水凝胶与3D打印植入物相结合的新产品。结果表明,该植入物能够通过减少初始爆发释放并随后持续释放,将sdAbs的释放维持长达13天。此外,配方筛选有助于确定最佳的sdAb配方条件,并增进了我们对CRS的理解。通过筛选步骤,我们了解了聚合物选择的影响以及sdAb与聚合物之间潜在的相互作用。总之,这项可行性研究证实了我们的CRS延长sdAb释放的能力,并确立了配方筛选对于最大化我们对CRS的了解所起的基本作用。