具有靶向识别和序贯治疗功能的纳米微球对血管化同种异体复合组织移植术后免疫抑制的研究
结题报告
批准号:
82002065
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
王守宝
依托单位:
学科分类:
体表组织器官移植与再造
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
王守宝
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中文摘要
血管化同种异体复合组织移植(VCA)是修复复杂组织缺损的理想方法,但VCA术后需每日应用多种免疫抑制剂,导致患者毒副作用明显和用药顺应性降低。缓释制剂可显著降低给药总量、延长给药间隔,但却存在明显突释现象。本项目拟通过改变药物包裹方式、负载具有靶向识别功能的MECA79和具有诱导功能的CD25单抗(Anti-CD25 mAb),构建出一种内部包裹他克莫司(FK506)和霉酚酸酯(MMF),外部负载Anti-CD25 mAb和MECA79的纳米微球。VCA术后局部注射该制剂,可通过MECA79靶向作用于移植物引流淋巴结,在此先由Anti-CD25 mAb发挥诱导治疗作用,然后随材料降解缓释出FK506和MMF发挥维持治疗作用。这种序贯治疗的方法最终起到显著延长移植物存活时间、缓解突释现象、降低药物毒副作用的效果。另外,探究该缓释制剂的释放规律和作用机制,将有助于开发高效、低毒的免疫抑制方案。
英文摘要
Vascularized composite allotransplantation (VCA) is an ideal for repairing complex tissue defects, however, daily administration of multiple immunosuppressants after VCA have severe side effects and reduce the compliance of VCA recipients. Sustained release system could significantly reduce drug dosage and eliminate daily systemic drug administration, but there are obvious burst releases. In this study, nanoparticles were internally encapsulated with tacrolimus (FK506) and mycophenolate mofetil (MMF) by changing the packaging method, externally loaded with anti-CD25 monoclonal antibody (Anti-CD25 mAb) for induction therapy and MECA79 for targeted recognition. Local injection of this sustained-release drug delivery system after VCA could target draining lymph nodes of the graft through MECA79, and it is first induced by anti-CD25 mAb, then FK506 and MMF are slowly released as the material degrades for maintenance therapy. The sequential therapy could prolong graft survival, alleviate burst release and minimize toxicity and complications. In addition, exploring the drug release pattern and mechanism of this sustained release system will help to develop efficient and low toxicity immuneosuppressive regimen in VCA.
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DOI:10.31083/j.fbl2710279
发表时间:2022-09
期刊:Frontiers in bioscience
影响因子:--
作者:Yuan Fang;Haibo Li;Ya Zhu;Jingting Chen;Yao Xiong;Xu Li;Binbin Sun;Shengli Li;L. Ye;Jianda Zhou;Shoubao Wang
通讯作者:Yuan Fang;Haibo Li;Ya Zhu;Jingting Chen;Yao Xiong;Xu Li;Binbin Sun;Shengli Li;L. Ye;Jianda Zhou;Shoubao Wang
DOI:10.1038/s41597-022-01577-y
发表时间:2022-09-07
期刊:SCIENTIFIC DATA
影响因子:9.8
作者:Fang, Yuan;Li, Haibo;Chen, Jingting;Xiong, Yao;Li, Xu;Sun, Binbin;Li, Shengli;Zhou, Jianda;Wang, Shoubao
通讯作者:Wang, Shoubao
Adipose-derived cellular therapies prolong graft survival in an allogenic hind limb transplantation model.
脂肪源性细胞疗法可延长同种异体后肢移植模型中的移植物存活率
DOI:10.1186/s13287-021-02162-7
发表时间:2021-01-29
期刊:Stem cell research & therapy
影响因子:7.5
作者:Chen J;Wang Y;Hu H;Xiong Y;Wang S;Yang J
通讯作者:Yang J
国内基金
海外基金