Faculty of Mathematics and Physics, University of Ljubljana, Jadranska 19, Ljubljana, Slovenia.
Biologics Drug Product, Technical Research and Development, Global Drug Development, Novartis, Lek d.d., Kolodvorska 27, Mengeš, Slovenia.
Colloids Surf B Biointerfaces. 2022 Oct;218:112757. doi: 10.1016/j.colsurfb.2022.112757. Epub 2022 Aug 5.
Monoclonal antibodies (mAbs) represent an important part of biological pharmaceutics. A serious challenge in their development is the formation of protein particles, which are often formed through protein aggregation at the air-liquid interface and then introduced into solution by interfacial stresses. In this paper, protein films formed at the air-liquid interface by two mAbs were disrupted by puncturing them with a microscopic needle, and the subsequent reconstitution of the film was observed in real-time by Brewster angle microscopy. Our results indicate that film reconstitution pace depends on mAb bulk concentration. Numerical modeling gives a quantitative prediction of the surface reconstitution. By extrapolating the model to concentrations typical for pharmaceutical formulations (>30 mg/mL) reconstitution timescales of the protein films can be estimated to be shorter than 0.01 s. Moreover, the effect of polysorbate 80 addition on protein film was studied. Film reconstitution measurements revealed that polysorbate 80 inhibits the film reconstitution process and breaks up the previously formed film.
单克隆抗体 (mAbs) 是生物制药的重要组成部分。在其开发过程中面临的一个严重挑战是蛋白质颗粒的形成，这些颗粒通常是通过在气液界面处的蛋白质聚集形成的，然后通过界面应力引入溶液中。在本文中，我们使用显微针刺破在气液界面形成的两种 mAb 的蛋白膜，并通过布鲁斯特角显微镜实时观察随后的膜重建。我们的结果表明，膜重建的速度取决于 mAb 的体相浓度。数值模型对表面重建进行了定量预测。通过将模型外推到药物制剂的典型浓度（>30mg/mL），可以估计蛋白质膜的重建时间尺度短于 0.01s。此外，还研究了聚山梨酯 80 对蛋白质膜的影响。膜重建测量表明，聚山梨酯 80 抑制了膜的重建过程并破坏了先前形成的膜。
