Development of mAb-loaded 3D-printed (FDM) implantable devices based on PLGA.
基于PLGA的载单克隆抗体3D打印（FDM）植入装置开发
📄 英文摘要 English Abstract
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.
📄 中文摘要 Chinese Abstract
📋 英文结构化总结 English Structured Summary
摘要整理
Background:
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.
Methods:
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.
Results:
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.
Data Summary:
The mAb-binding capacity was preserved up to 70% following the whole fabrication process. The 3D-printed devices showed sustained-release profiles with a low burst effect.
Conclusions:
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.
Practical Significance:
These promising results demonstrate that FDM could be used to produce mAb-loaded devices with good stability, affinity and sustained-release profiles, indicating potential real-world applications for implantable systems.
📋 中文结构化总结 Chinese Structured Summary
背景:
本研究的主要目标是探索利用熔融沉积建模（FDM）技术打印载单克隆抗体（mAb）植入系统的可行性，以构建复杂的剂型设计。据我们所知，这是首次利用FDM技术开展载mAb装置的研究。
方法:
为实现这一目标，研究对多个步骤进行了开发与优化。首先使用海藻糖（TRE）、蔗糖（SUC）、羟丙基-β-环糊精（HP-β-CD）、山梨醇或菊粉（INU）对mAb溶液进行稳定化处理，随后进行喷雾干燥（SD）。然后采用热熔挤出（HME）技术，以丙交酯-乙交酯共聚物（PLGA）和mAb粉末（15% w/w）制备可打印丝材。对FDM工艺进行了优化，以确保在打印过程中不影响mAb的稳定性。最终选择TRE并与L-亮氨酸（LEU）联合使用，以进一步提高mAb的稳定性。
结果:
随后通过高分子量和低分子量物种水平对稳定性进行评估。结果表明，所选赋形剂在HME和FDM两个工艺过程中均能有效稳定mAb。3D打印装置表现出缓释特性，且突释效应较低。在整个制备工艺完成后，mAb的结合能力保留率高达70%。
数据总结:
在整个制备工艺完成后，mAb的结合能力保留率高达70%。3D打印装置表现出缓释特性，且突释效应较低。
结论:
这些令人鼓舞的结果表明，FDM技术可用于制备具有良好稳定性、亲和力及缓释特性的载mAb装置。
实际意义:
这些令人鼓舞的结果表明，FDM技术可用于制备具有良好稳定性、亲和力及缓释特性的载mAb装置，显示出植入系统在实际应用中的巨大潜力。