Delivery of FK506-loaded PLGA nanoparticles prolongs cardiac allograft survival
Delivery of FK506-loaded PLGA nanoparticles prolongs cardiac allograft survival
复制标题
负载 FK506 的 PLGA 纳米颗粒的递送可延长同种异体心脏移植物的存活率。
DOI：
10.1016/j.ijpharm.2019.118951
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发表时间：
2020-02-15
影响因子：
5.8
通讯作者：
Xie, Mingxing
中科院分区：
文献类型：
--
作者：
Deng, Cheng;Chen, Yihan;Xie, Mingxing
在这项研究中，FK 506负载聚（丙交酯-共-乙交酯）纳米粒子（PLGA-FK 506-NPs）的开发使用O/W乳液溶剂蒸发法。通过透射和扫描电子显微镜观察到PLGA-FK 506-NP是单分散的和球形的。通过动态光散射测量的平均尺寸和zeta电位分别为110 +/- 1.3 nm和-20.56 +/- 3.65 mV。FK 506的包封率和装载率分别为94.46 +/- 1.88%和5.38 +/-0.24%。此外，药代动力学研究显示，PLGA-FK 506-NP表现出与游离FK 506显著不同，表现出更高的曲线下面积（1.69倍）、更高的平均滞留时间（1.29倍）、更慢的清除率和更长的消除半衰期。值得注意的是，PLGA-FK 506-NP组脾脏和肠系膜淋巴结中FK 506的浓度分别是游离FK 506组的3.1倍和2.9倍。此外，在大鼠异位心脏移植模型中评估了免疫抑制效果，结果显示，与游离FK 506治疗相比，PLGA-FK 506-NP治疗可成功缓解急性排斥反应并延长同种异体移植物存活时间（平均存活时间，17.1 +/- 2.0 vs 13.3 +/- 1.7天）。总之，PLGA-FK 506-NPs是一种有前途的脾和淋巴结递送制剂，并在心脏移植物急性排斥反应的治疗中具有潜在的用途。
In this study, FK506-loaded poly(lactide-co-glycolide) nanoparticles (PLGA-FK506-NPs) were developed using an O/W emulsion solvent evaporation method. The PLGA-FK506-NPs were observed to be monodispersed and spherical by transmission and scanning electron microscopy. The mean size and zeta potential measured by dynamic light scattering were 110 +/- 1.3 nm and -20.56 +/- 3.65 mV, respectively. The FK506 entrapment and loading efficiency were 94.46 +/- 1.88% and 5.38 +/- 0.24%, respectively. Moreover, a pharmacokinetics study revealed that the PLGA-FK506-NPs behaved significantly different than free FK506 by exhibiting a higher area under curve (1.69-fold), higher mean residence time (1.29-fold), slower clearance and longer elimination half-life. Notably, the concentrations of FK506 in the spleen and mesenteric lymph nodes of the PLGA-FK506-NP group were 3.1-fold and 2.9-fold higher than those of the free FK506 group. Furthermore, the immunosuppressive efficacy was evaluated in a rat heterotopic heart transplantation model, and the results showed that PLGA-FK506-NP treatment could successfully alleviate acute rejection and prolong allograft survival compared with the free FK506 treatment (mean survival time, 17.1 +/- 2.0 versus 13.3 +/- 1.7 days). In conclusion, PLGA-FK506-NPs are a promising formulation for spleen and lymph node delivery and have potential use in the treatment of cardiac allograft acute rejection.