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对PGP进行表面修饰以制备中性粒细胞-纳米颗粒共载体,增强黄芩苷的抗抑郁作用。

Surface modification of PGP for a neutrophil-nanoparticle co-vehicle to enhance the anti-depressant effect of baicalein.

作者信息

Chen Baoyu, Luo Man, Liang Jianming, Zhang Chun, Gao Caifang, Wang Jue, Wang Jianxin, Li Yongji, Xu Desheng, Liu Lina, Zhang Ning, Chen Huijun, Qin Jing

机构信息

Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Department of Pharmaceutics, School of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.

出版信息

Acta Pharm Sin B. 2018 Jan;8(1):64-73. doi: 10.1016/j.apsb.2017.11.012. Epub 2017 Dec 29.

Abstract

Exploiting cells as vehicles combined with nanoparticles combined with therapy has attracted increasing attention in the world recently. Red blood cells, leukocytes and stem cells have been used for tumor immunotherapy, tissue regeneration and inflammatory disorders, and it is known that neutrophils can accumulate in brain lesions in many brain diseases including depression. -Acetyl Pro-Gly-Pro (PGP) peptide shows high specific binding affinity to neutrophils through the CXCR2 receptor. In this study, PGP was used to modify baicalein-loaded solid lipid nanoparticles (PGP-SLNs) to facilitate binding to neutrophils . Brain-targeted delivery to the basolateral amygdala (BLA) was demonstrated by enhanced concentration of baicalein in the BLA. An enhanced anti-depressant effect was observed and The mechanism involved inhibition of apoptosis and a decrease in lactate dehydrogenase release. Behavioral evaluation carried out with rats demonstrated that anti-depression outcomes were achieved. The results indicate that PGP-SLNs decrease immobility time, increase swimming time and climbing time and attenuate locomotion in olfactory-bulbectomized (OB) rats. In conclusion, PGP modification is a strategy for targeting the brain with a cell-nanoparticle delivery system for depression therapy.

摘要

将细胞作为载体与纳米颗粒及治疗方法相结合,近来在全球受到越来越多的关注。红细胞、白细胞和干细胞已被用于肿瘤免疫治疗、组织再生和炎症性疾病,并且已知在包括抑郁症在内的许多脑部疾病中,中性粒细胞可在脑损伤部位积聚。-乙酰基脯氨酰-甘氨酰-脯氨酸(PGP)肽通过CXCR2受体对中性粒细胞表现出高特异性结合亲和力。在本研究中,PGP被用于修饰载有黄芩苷的固体脂质纳米粒(PGP-SLNs),以促进与中性粒细胞的结合。通过黄芩苷在基底外侧杏仁核(BLA)中浓度的升高,证明了其向BLA的脑靶向递送。观察到抗抑郁作用增强,其机制涉及抑制细胞凋亡和降低乳酸脱氢酶释放。对大鼠进行的行为评估表明实现了抗抑郁效果。结果表明,PGP-SLNs减少了嗅球切除(OB)大鼠的不动时间,增加了游泳时间和攀爬时间,并减弱了运动能力。总之,PGP修饰是一种利用细胞-纳米颗粒递送系统靶向脑部进行抑郁症治疗的策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2b9/5985696/9dd3c314b099/gr1.jpg

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