Red blood cell membrane-camouflaged poly(lactic-co-glycolic acid) microparticles as a potential controlled release drug delivery system for local stellate ganglion microinjection.
Red blood cell membrane-camouflaged poly(lactic-co-glycolic acid) microparticles as a potential controlled release drug delivery system for local stellate ganglion microinjection.
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DOI：
10.1016/j.actbio.2023.02.030
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发表时间：
2023-02
影响因子：
9.7
通讯作者：
Bo Liu;Dongze Zhang;H. Tu;O. A. Alimi;Yunfan Kong;Rachagani Satyanarayana;Mitchell A. Kuss;
中科院分区：
文献类型：
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作者：
Bo Liu;Dongze Zhang;H. Tu;O. A. Alimi;Yunfan Kong;Rachagani Satyanarayana;Mitchell A. Kuss;
星状神经节（SG）是交感神经系统的一部分，对人体上半身的几个组织和器官具有重要的调节作用。SG阻滞和干预已在临床和临床前实施，以管理上肢、颈部、头部和上胸部的慢性疼痛以及慢性心力衰竭。然而，已经有非常有限的努力，以开发和研究基于聚合物的药物递送系统，用于局部递送到SG。在这项研究中，我们制作了红细胞（RBC）膜包裹的聚（乳酸-羟基乙酸）（PLGA）（PLGAM）微粒作为一个潜在的长期控制释放系统的局部药物输送。结构，尺寸和表面zeta电位的结果表明，球形PLGAM微粒成功地制造。PLGA和PLGAM微粒均表现出与人脂肪间充质干细胞（ADMSC）和卫星胶质细胞的生物相容性，并显示出血液相容性。此外，PLGA和PLGAM对体外培养的人单核细胞源性巨噬细胞分泌促炎细胞因子无明显影响。我们将微粒显微注射到大鼠SG中，并在21天内评估微粒的保留时间和微粒对体内炎症的影响。随后，我们使用集落刺激因子-1受体抑制剂GW 2580作为模型药物制备载药PLGAM微粒，并评估其包封率、药物释放曲线、生物相容性和体外抗炎效果。我们的研究结果表明，PLGAM微粒的长期控制的局部药物释放在SG.Statement的significanceSG块通过局部注射治疗抑制交感神经的活动提供了一个有价值的好处，以管理慢性疼痛和慢性心力衰竭的潜力。我们描述了红细胞膜包裹的PLGA微粒的细胞相容性，血液相容性和低免疫原性的制造，并证明他们可以成功和安全地显微注射到大鼠SG。微粒在SG内的保留时间超过21天，而不会引起可检测的炎症。此外，我们将CSF-1 R抑制剂作为模型药物，并证明了长期药物释放和调节巨噬细胞功能的能力。这些策略证明了将载有治疗剂的微粒局部微注射到SG中的可行性，并为进一步的疗效和疾病治疗评估铺平了道路。
The stellate ganglion (SG) is a part of the sympathetic nervous system that has important regulatory effects on several human tissues and organs in the upper body. SG block and intervention have been clinically and preclinically implemented to manage chronic pain in the upper extremities, neck, head, and upper chest as well as chronic heart failure. However, there has been very limited effort to develop and investigate polymer-based drug delivery systems for local delivery to the SG. In this study, we fabricated red blood cell (RBC) membrane-camouflaged poly(lactic-co-glycolic acid) (PLGA) (PLGAM) microparticles for use as a potential long-term controlled release system for local drug delivery. The structure, size, and surface zeta potential results indicated that the spherical PLGAM microparticles were successfully fabricated. Both PLGA and PLGAM microparticles exhibited biocompatibility with human adipose mesenchymal stem cells (ADMSC) and satellite glial cells and showed hemocompatibility. In addition, both PLGA and PLGAM displayed no significant effects on the secretion of proinflammatory cytokines by human monocyte derived macrophagesin vitro. We microinjected microparticles into rat SGs and evaluated the retention time of microparticles and the effects of the microparticles on inflammationin vivoover 21 days. Subsequently, we fabricated drug-loaded PLGAM microparticles by using GW2580, a colony stimulating factor-1 receptor inhibitor, as a model drug and assessed its encapsulation efficiency, drug release profiles, biocompatibility, and anti-inflammatory effectsin vitro. Our results demonstrated the potential of PLGAM microparticles for long-term controlled local drug release in the SG.Statement of significanceSG block by locally injecting therapeutics to inhibit the activity of the sympathetic nerves provides a valuable benefit to manage chronic pain and chronic heart failure. We describe the fabrication of RBC membrane-camouflaged PLGA microparticles with cytocompatibility, hemocompatibility, and low immunogenicity, and demonstrate that they can be successfully and safely microinjected into rat SGs. The microparticle retention time within SG is over 21 days without eliciting detectable inflammation. Furthermore, we incorporate a CSF-1R inhibitor as a model drug and demonstrate the capacities of long-term drug release and regulation of macrophage functions. The strategies demonstrate the feasibility to locally microinject therapeutics loaded microparticles into SGs and pave the way for further efficacy and disease treatment evaluation.