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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 mAbloaded devices with good stability, affinity and sustained-release profiles of the mAb.

A B S T R A C TIn this study, the possibility of producing highly antibody-loaded microparticles with sustained-release properties was evaluated. Polyclonal immunoglobulin G (IgG) was used as a model of antibody and its encapsulation into poly(lactide-co-glycolide) acid (PLGA) microparticles was performed by spray-drying a water-in-oil (w/o) emulsion. It was demonstrated that the use of the Resomer ® RG505 PLGA allowed an IgG loading of 20% w/w with an encapsulation efficiency higher than 85%. The produced microparticles were characterized by a mean diameter lower than 10 µm. The burst effect was shown to reach a maximal value of 40%. IgG stability after encapsulation was also assessed. The use of this single PLGA provided a lag time of 3 months which dramatically slowed down the release rate after the initial release of the encapsulated IgG. Using blends of PLGA characterized by different inherent viscosities allowed decreasing the lag time and modulating the dissolution profile of the IgG from the spray-dried microparticles. Therefore, spray-drying a water-in-oil emulsion appeared to be a promising strategy to produce highly antibody-loaded microparticles characterized by sustained-release properties.