UEA I-bearing nanoparticles for brain delivery following intranasal administration
UEA I-bearing nanoparticles for brain delivery following intranasal administration
复制标题
载有 UEA I 的纳米粒子用于鼻内给药后的脑递送
DOI：
10.1016/j.ijpharm.2007.03.039
复制
发表时间：
2007-08-01
影响因子：
5.8
通讯作者：
Jiang, Xinguo
中科院分区：
文献类型：
--
作者：
Gao, Xiaoling;Chen, Jun;Jiang, Xinguo
含有凝集素的纳米颗粒的表面工程开辟了一条新的途径，以改善鼻腔给药后可生物降解的聚乙二醇-聚乳酸纳米颗粒负载的药物的大脑摄取。选择特异性结合L-病灶的欧洲Ulex凝集素I （UEA I）作为一种有前景的靶向配体，利用马来酰亚胺介导的共价结合技术优化方案，将其偶联到PEG-PLA纳米颗粒表面。大鼠体内实验结果表明，纳米颗粒表面的UEA I修饰促进了与纳米颗粒相关的荧光标记-6-香豆素在鼻内给药后进入大脑的吸收，与未修饰的香豆素相比，浓度-时间曲线下的脑组织面积显著增加（约1.7倍）。UEA i偶联也提高了纳米颗粒的脑靶向效率。特异性糖的抑制实验表明，凝集纳米颗粒与鼻黏膜的相互作用是由于纳米颗粒表面固定了碳水化合物结合袋。UEA i修饰纳米颗粒的分布特征表明其对嗅觉粘膜的亲和性高于对呼吸粘膜的亲和性。因此，UEA i修饰的纳米颗粒可能成为脑药物递送的潜在载体，特别是具有多种生物效应的精神治疗。(c) 2007年Elsevier B.V.出版
Surface engineering of nanoparticles with lectins opened a novel pathway to improve the brain uptake of agents loaded by biodegradable PEG-PLA nanoparticles following intranasal administration. Ulex europeus agglutinin I (UEA I), specifically binding to L-fucose, which is largely located in the olfactory epithelium, was selected as a promising targeting ligand and conjugated onto the PEG-PLA nanoparticles surface with an optimized protocol relying on maleimide-mediated covalent binding technique. The in vivo results in rats suggested that UEA I modification at the nanoparticles surface facilitated the absorption of a fluorescent marker-6-coumarin associated with the nanoparticles into the brain following intranasal administration with significant increase in the area under the concentration-time curve (about 1.7 times) indifferent brain tissues compared with that of coumarin incorporated in the unmodified ones. UEA I-conjugation also elevated the brain-targeting efficiency of nanoparticles. Inhibition experiment of specific sugar suggested that the interactions between the nasal mucosa and the lectinised nanoparticles were due to the immobilization of carbohydrate-binding pockets on the surface of the nanoparticles. Distribution profiles of UEA I-modified nanoparticles indicated their higher affinity to the olfactory mucosa than to the respiratory one. Therefore, the UEA I-modified nanoparticles might serve as potential carriers for brain drug delivery, especially for mental therapeutics with multiple biological effects. (c) 2007 Published by Elsevier B.V.