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通过氧纳米气泡有效递送霉酚酸以调节免疫抑制。

Effective delivery of mycophenolic acid by oxygen nanobubbles for modulating immunosuppression.

作者信息

Khan Muhammad Saad, Kim Jae-Sung, Hwang Jangsun, Choi Yonghyun, Lee Kyungwoo, Kwon Yejin, Jang Jaehee, Yoon Semi, Yang Chul-Su, Choi Jonghoon

机构信息

School of Integrative Engineering, Chung-Ang University, Seoul 06974, Republic of Korea.

Department of Bionano Technology, Hanyang University, Seoul 04673, Republic of Korea.

出版信息

Theranostics. 2020 Mar 4;10(9):3892-3904. doi: 10.7150/thno.41850. eCollection 2020.

Abstract

Immunosuppressive drugs are crucial for preventing acute graft rejection or autoimmune diseases. They are generally small molecules that require suitable drug carriers for ensuring stability, bioavailability, and longer half-life. Mycophenolic acid (MPA) is an extensively studied immunosuppressive drug. However, it requires suitable carriers for overcoming clinical limitations. Currently, lipid-shelled micro- and nanobubbles are being thoroughly investigated for diagnostic and therapeutic applications, as they possess essential properties, such as injectability, smaller size, gaseous core, high surface area, higher drug payload, and enhanced cellular penetration. Phospholipids are biocompatible and biodegradable molecules, and can be functionalized according to specific requirements. : In this study, we synthesized oxygen nanobubbles (ONBs) and loaded the hydrophobic MPA within the ONBs to generate ONB/MPA. Peripheral blood mononuclear cells (PBMCs) were treated with ONB/MPA to determine the suppression of immune response by measuring cytokine release. murine experiments were performed to evaluate the effectiveness of ONB/MPA in the presence of inflammatory stimulants. : Our results suggest that ONBs successfully delivered MPA and reduced the release of cytokines, thereby controlling inflammation and significantly increasing the survival rate of animals. : This method can be potentially used for implantation and for treating autoimmune diseases, wherein immunosuppression is desired.

摘要

免疫抑制药物对于预防急性移植排斥反应或自身免疫性疾病至关重要。它们通常是小分子,需要合适的药物载体来确保稳定性、生物利用度和更长的半衰期。霉酚酸(MPA)是一种经过广泛研究的免疫抑制药物。然而,它需要合适的载体来克服临床局限性。目前,脂质壳微泡和纳米泡正在被深入研究用于诊断和治疗应用,因为它们具有诸如可注射性、尺寸更小、气态核心、高表面积、更高的药物负载量和增强的细胞穿透性等基本特性。磷脂是生物相容性和可生物降解的分子,并且可以根据特定要求进行功能化。在本研究中,我们合成了氧纳米泡(ONBs)并将疏水性的MPA负载到ONBs中以生成ONB/MPA。用ONB/MPA处理外周血单核细胞(PBMCs),通过测量细胞因子释放来确定免疫反应的抑制情况。进行小鼠实验以评估在存在炎症刺激物的情况下ONB/MPA的有效性。我们的结果表明,ONBs成功递送了MPA并减少了细胞因子的释放,从而控制了炎症并显著提高了动物的存活率。这种方法可能潜在地用于植入和治疗需要免疫抑制的自身免疫性疾病。

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