Laboratory of Pharmaceutics and Biopharmaceutics, Université libre de Bruxelles, Faculty of Pharmacy, 1050 Brussels, Belgium.
Department of Biological Pharmaceutical Sciences, UCB Pharma S.A, 1420 Braine-l'Alleud, Belgium.
Int J Pharm. 2021 Mar 15;597:120337. doi: 10.1016/j.ijpharm.2021.120337. Epub 2021 Feb 4.
The main objective of this work was to explore the feasibility to print monoclonal antibody (mAb)-loaded implantable systems using fused-deposition modelling (FDM) to build complex dosage form designs. Indeed, to our knowledge, this work is the first investigation of mAb-loaded devices using FDM. To make this possible, different steps were developed and optimized. A mAb solution was stabilized using trehalose (TRE), sucrose (SUC), hydroxypropyl-β-cyclodextrin (HP-β-CD), sorbitol or inulin (INU) in order to be spray dried (SD). Printable filaments were then made of poly(lactide-co-glycolide) (PLGA) and mAb powder (15% w/w) using hot melt extrusion (HME). The FDM process was optimized to print these filaments without altering the mAb stability. TRE was selected and associated to L-leucine (LEU) to increase the mAb stability. The stability was then evaluated considering high and low molecular weight species levels. The mAb-based devices were well-stabilized with the selected excipients during both the HME and the FDM processes. The 3D-printed devices showed sustained-release profiles with a low burst effect. The mAb-binding capacity was preserved up to 70% following the whole fabrication process. These promising results demonstrate that FDM could be used to produce mAb-loaded devices with good stability, affinity and sustained-release profiles of the mAb.
这项工作的主要目的是探索使用熔融沉积建模（FDM）打印载单抗（mAb）的可植入系统的可行性，以构建复杂的剂型设计。事实上，据我们所知，这是首次使用 FDM 研究载 mAb 的装置。为了实现这一目标，开发并优化了不同的步骤。使用海藻糖（TRE）、蔗糖（SUC）、羟丙基-β-环糊精（HP-β-CD）、山梨糖醇或菊粉（INU）稳定 mAb 溶液，然后通过喷雾干燥（SD）制成可印刷的纤维。然后使用热熔挤出（HME）由聚（乳酸-共-乙醇酸）（PLGA）和 mAb 粉末（15%w/w）制成可打印的纤维。优化了 FDM 工艺，以在不改变 mAb 稳定性的情况下打印这些纤维。选择 TRE 并与 L-亮氨酸（LEU）结合使用，以提高 mAb 的稳定性。然后考虑高分子量和低分子量物质的水平来评估稳定性。在 HME 和 FDM 过程中，选择的赋形剂使基于 mAb 的装置得到了很好的稳定。3D 打印的装置显示出具有低突释效应的持续释放曲线。在整个制造过程中，mAb 结合容量保持在 70%左右。这些有希望的结果表明，FDM 可用于生产具有良好稳定性、亲和力和 mAb 持续释放曲线的载 mAb 装置。
