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E-选择素结合肽修饰牛血清白蛋白纳米颗粒治疗急性肺损伤。

E-Selectin-Binding Peptide-Modified Bovine Serum Albumin Nanoparticles for the Treatment of Acute Lung Injury.

机构信息

Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, Chengdu, People's Republic of China.

Department of Obstetrics and Gynecology, West China Second University Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.

出版信息

AAPS PharmSciTech. 2019 Jul 30;20(7):270. doi: 10.1208/s12249-019-1403-2.

Abstract

Currently, there is no specific treatment for acute lung injury (ALI). E-selectin-binding peptide (Esbp), a high-affinity peptide that delivers drugs targeting inflammatory vascular endothelial cells, can bind to E-selectin and act as a targeting ligand for selective drug delivery. In this study, we coupled the thiol groups of Esbp to the amino groups on the surface of bovine serum albumin (BSA) using succinimidyl iodoacetic acid to make Esbp-modified BSA nanoparticles (BSANPs) at the average ratio of 19.3 μg Esbp to 1 mg BSA. The Esbp-modified BSANPs were spherical in shape and had a particle size of 266.7 ± 2.7 nm, polydispersity index of 0.165 ± 0.02, zeta potential of - 33.64 ± 1.23 mV, encapsulation efficiency of 84.3 ± 2.3%, and drug loading of 6.7 ± 0.32%. The cumulative release rate of dexamethasone-loaded Esbp-modified BSANPs was 51.2% within 12 h, significantly lower than that of 88.2% of free drugs. Moreover, Esbp-modified BSANPs could be uptaken in vitro by activated human umbilical vein endothelial cells and in vivo by the lungs of the established ALI mouse model. These results indicated that our Esbp-modified BSANPs delivery system has characteristics of good targeting ability and biocompatibility and is able to inhibit inflammation. Overall, our Esbp-modified BSANPs delivery system has therapeutic potentials as a new targeting drug system for the treatment of ALI in the future.

摘要

目前,急性肺损伤(ALI)尚无特异性治疗方法。E-选择素结合肽(Esbp)是一种高亲和力的肽,可将靶向炎症血管内皮细胞的药物递送至炎症部位,可与 E-选择素结合,作为靶向配体用于选择性药物传递。在这项研究中,我们使用琥珀酰亚胺碘乙酰胺将 Esbp 的巯基与牛血清白蛋白(BSA)表面的氨基连接起来,使 Esbp 修饰的 BSA 纳米颗粒(BSANPs)的平均比例为 19.3μg Esbp 与 1mg BSA。Esbp 修饰的 BSANPs 呈球形,粒径为 266.7±2.7nm,多分散指数为 0.165±0.02,Zeta 电位为-33.64±1.23mV,包封率为 84.3±2.3%,载药量为 6.7±0.32%。在 12 小时内,载地塞米松的 Esbp 修饰的 BSANPs 的累积释放率为 51.2%,明显低于游离药物的 88.2%。此外,Esbp 修饰的 BSANPs 可在体外被激活的人脐静脉内皮细胞摄取,在体内被建立的 ALI 小鼠模型的肺部摄取。这些结果表明,我们的 Esbp 修饰的 BSANPs 递药系统具有良好的靶向能力和生物相容性,能够抑制炎症。总的来说,我们的 Esbp 修饰的 BSANPs 递药系统具有作为未来治疗 ALI 的新型靶向药物系统的治疗潜力。

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