Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi, 467-8603, Japan.
AAPS J. 2023 Sep 22;25(6):92. doi: 10.1208/s12248-023-00859-6.
Poly lactic-co-glycolic acid (PLGA) microparticles have been formulated to allow the sustained release of numerous drugs, including antibodies. It is well-known that antibodies are susceptible to chemical and physical stress; therefore, it is necessary to be loaded on PLGA microparticles under mild conditions. In the present study, we constructed cationic porous PLGA microparticles that could be electrostatically adsorbed with infliximab as a model antibody. Cationic porous PLGA microparticles were prepared using the double emulsion method by adding polyethyleneimine and ammonium bicarbonate. After antibody loading, surface pores closure was achieved by mild heating. The size of the optimized formulation was approximately 5 μm, exhibiting a positive charge. The loaded antibody was gradually released from the formulation over 56 days. Based on a tumor necrosis factor (TNF)-α inhibition assay, the released infliximab maintained its pharmacological activity. Collectively, we successfully loaded antibodies into PLGA microparticles while maintaining activity and demonstrating long-acting properties.
聚乳酸-共-羟基乙酸(PLGA)微球已被制成可使多种药物(包括抗体)持续释放。众所周知,抗体易受化学和物理压力的影响;因此,有必要在温和条件下将其负载于 PLGA 微球上。在本研究中,我们构建了阳离子多孔 PLGA 微球,可将英夫利昔单抗作为模型抗体通过静电吸附作用加载到微球上。阳离子多孔 PLGA 微球是通过加入聚乙烯亚胺和碳酸氢铵,采用双重乳液法制备的。在加载抗体后,通过温和加热实现表面孔的闭合。优化后的制剂粒径约为 5μm,带正电荷。负载的抗体可在 56 天内逐渐从制剂中释放出来。基于肿瘤坏死因子(TNF)-α抑制测定,释放的英夫利昔单抗保持了其药理活性。总之,我们成功地将抗体负载到 PLGA 微球中,同时保持了其活性并显示出长效特性。