Development of mAb-loaded 3D-printed (FDM) implantable devices based on PLGA.

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.