Development and effects of tacrolimus-loaded nanoparticles on the inhibition of corneal allograft rejection
Development and effects of tacrolimus-loaded nanoparticles on the inhibition of corneal allograft rejection
复制标题
他克莫司纳米粒的研制及其抑制角膜移植排斥反应的效果
DOI：
10.1080/10717544.2019.1582728
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发表时间：
2019-01-01
期刊：
影响因子：
6
通讯作者：
Lin, Haotian
中科院分区：
文献类型：
--
作者：
Wu, Qianni;Liu, Dong;Lin, Haotian
摘要他克莫司已被广泛应用于器官移植术后预防排斥反应。然而，他克莫司的常规药物制剂由于其疏水性和低角膜穿透性而限制了其在眼部治疗中的应用。我们通过简单有效的纳米技术优化了他克莫司甲氧基聚（乙二醇-嵌段-聚（d，l）-乳酸-羟基乙酸）纳米粒（TAC-NPs）作为角膜移植排斥反应的药物递送系统，以克服这些缺点。制备的纳米粒粒径为82.9 ± 1.3 nm，载药量为8.01 ± 0.23%，包封率为80.10 ± 2.33%。此外，使用新西兰兔，使用高效液相色谱串联质谱法（HPLC-MS/MS）分析TAC-NPs的单次给药药代动力学。在同种异体穿透性角膜移植术的大鼠中，与常规的0.1%他克莫司滴剂相比，TAC-NPs分散滴剂的施用改善了房水和角膜中的TAC浓度，这与对IL-2、IL-17和VEGF表达的显著更高的有效抑制一致。同时，我们还比较了TAC-NPs的两种不同的局部给药方法（包括滴眼和结膜下注射），以最大限度地发挥NPs的缓释特性。总之，小粒径的TAC-NPs增强了TAC的经角膜渗透和吸收，更有效地抑制了角膜移植排斥反应，表明基于可生物降解聚合物纳米材料的药物递送系统在提高疏水性药物的临床治疗效果方面具有巨大潜力。
Abstract Tacrolimus has been widely applied to prevent organ rejection after transplantation. However, the conventional pharmaceutical formulation of tacrolimus limits its applications in ocular therapy due to its hydrophobicity and low corneal penetrability. We optimized tacrolimus-loaded methoxy poly (ethylene glycol-block-poly (d, l)-lactic-co-glycolic acid) nanoparticles (TAC-NPs) by simple and effective nanotechnology as a drug delivery system for corneal graft rejection to overcome these drawbacks. The prepared TAC-NPs were 82.9 ± 1.3 nm in size, and the drug loading and encapsulation efficiency were 8.01 ± 0.23% and 80.10 ± 2.33%. Furthermore, New Zealand rabbits were used to analyze the single-dose pharmacokinetics of the TAC-NPs using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). In rats with allogenic penetrating keratoplasty, the administration of TAC-NPs dispersion drops improved the TAC concentrations in the aqueous humor and cornea, consistent with a significantly higher effective inhibition of IL-2, IL-17, and VEGF expression compared with conventional 0.1% tacrolimus drops. Meanwhile, we also compared two different topical administration methods (including eye drop and subconjunctival injection) of TAC-NPs to maximize the sustained release characteristic of NPs. In summary, the small-sized TAC-NPs enhanced transcorneal permeation and absorption of TAC and more effectively inhibited corneal allograft rejection, which indicated that biodegradable polymeric nanomaterials-based drug delivery system had great potential for improving the clinical therapy efficacy of hydrophobic drugs.