Using Gelatin Nanoparticle Mediated Intranasal Delivery of Neuropeptide Substance P to Enhance Neuro-Recovery in Hemiparkinsonian Rats.
Using Gelatin Nanoparticle Mediated Intranasal Delivery of Neuropeptide Substance P to Enhance Neuro-Recovery in Hemiparkinsonian Rats.
复制标题
使用明胶纳米颗粒介导的神经肽 P 物质鼻内递送来增强偏侧帕金森病大鼠的神经恢复
DOI：
10.1371/journal.pone.0148848
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Lu CT
中科院分区：
文献类型：
--
作者：
Zhao YZ;Jin RR;Yang W;Xiang Q;Yu WZ;Lin Q;Tian FR;Mao KL;Lv CZ;Wáng YX;Lu CT
制备了以磷脂为基础的明胶纳米颗粒（GNP）鼻内给药，研究了神经肽P物质（SP）对半帕金森大鼠的神经恢复作用。采用水包水乳化法制备了SP-GNP纳米粒，具有较高的稳定性、包封效率和负载能力。采用MTT法和流式细胞术（FCM）检测PC-12细胞对SP-GNP的体外生长促进作用。通过定量旋转行为及黑质（SN）区酪氨酸羟化酶（TH）、磷酸化c-Jun蛋白（p-c-Jun）、Caspase-3 （Cas-3）表达水平，评价SP-GNP对6-羟多巴胺（6-OHDA）诱导的偏帕金森大鼠的治疗作用。SP- gnp处理的PC-12细胞比SP溶液处理的细胞存活率高，凋亡程度低。与鼻用SP溶液和静脉注射SP- gnp组相比，鼻用SP- gnp组大鼠表现出更好的行为改善，SN中TH水平升高，p-c-Jun和Cas-3水平明显降低。SP具有GNP和鼻-脑通路的优势，可通过抑制JNK通路和多巴胺能神经元凋亡，有效地将其输送到受损的SN区，发挥其神经恢复功能。
Intranasal administration of phospholipid-based gelatin nanoparticles (GNP) was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP) on hemiparkinsonian rats. The SP-loaded gelatin nanoparticles (SP-GNP) were prepared by a water-in-water emulsion method and possessed high stability, encapsulating efficiency and loading capacity. PC-12 cells were used to examine the growth enhancement of SP-GNP in vitro by MTT assays and flow cytometry (FCM). The therapeutic effects of SP-GNP on 6-hydroxydopamine (6-OHDA) induced hemiparkinsonian rats were assessed by quantifying rotational behavior and the levels of tyrosine hydroxylase (TH), phosphorylated c-Jun protein (p-c-Jun) and Caspase-3 (Cas-3) expressed in substantia nigra (SN) region of hemiparkinsonian rats. PC-12 cells under SP-GNP treatment showed better cell viability and lower degree of apoptosis than those under SP solution treatment. Hemiparkinsonian rats under intranasal SP-GNP administration demonstrated better behavioral improvement, higher level of TH in SN along with much lower extent of p-c-Jun and Cas-3 than those under intranasal SP solution administration and intravenous SP-GNP administration. With the advantages of GNP and nose-to-brain pathway, SP can be effectively delivered into the damaged SN region and exhibit its neuro-recovery function through the inhibition on JNK pathway and dopaminergic neuron apoptosis.