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

被引:16
作者
Liu, Yu [1 ]
Yang, Bowen [2 ,3 ,4 ]
Zhao, Xuan [1 ]
Xi, Mingrong [2 ,3 ,4 ]
Yin, Zongning [1 ]
机构
[1] Sichuan Univ, West China Sch Pharm, Key Lab Drug Targeting & Drug Delivery Syst, Chengdu, Sichuan, Peoples R China
[2] Sichuan Univ, West China Univ Hosp 2, Dept Obstet & Gynecol, Chengdu 610041, Sichuan, Peoples R China
[3] Sichuan Univ, Minist Educ, Key Lab Birth Defects & Related Dis Women & Child, Chengdu, Sichuan, Peoples R China
[4] Sichuan Univ Chengdu, West China Univ Hosp 2, Minist Educ, Chengdu, Sichuan, Peoples R China
基金
中国国家自然科学基金;
关键词
acute lung injury; E-selectin-binding peptide; dexamethasone; bovine serum albumin nanoparticles; targeting ability; MICELLES; DEXAMETHASONE; DYSFUNCTION; EXPRESSION; CONJUGATE; COPOLYMER; DELIVERY; PHAGE; ARDS; CELL;
D O I
10.1208/s12249-019-1403-2
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mu g Esbp to 1mg BSA. The Esbp-modified BSANPs were spherical in shape and had a particle size of 266.7 +/- 2.7nm, polydispersity index of 0.165 +/- 0.02, zeta potential of -33.64 +/- 1.23mV, 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 12h, 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.
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页数:11
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