A novel nanocomposite Lf-DA-MSN-PF127 aided the delivery of dopamine for the treatment of Parkinson's disease in a rat model

IF 4.6 3区 材料科学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Ramesha Hanumanthappa, Sumit Ramesh Naik, Sahana Prakash Nayak, Asmatanzeem Bepari, Hanan Nasser Altamimi, Mujeeb Ahmed Shaikh, Fahd A. Nasr, Farha M. Shaikh, P. C. Nethravathi, Hemalatha Nanjaiah, D. Suresh, Raghu S. V. and Kuramkote Shivanna Devaraju
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Abstract

Dopamine is a pivotal neurotransmitter in the central nervous system, which is instrumental in motor functions. Parkinson's Disease (PD) is a chronic, progressive, age-related neurodegenerative disorder marked by the progressive loss of dopaminergic neurons in the pars compacta of the substantia nigra in the midbrain, resulting in the reduction of dopamine levels. Levodopa is a prescribed medicine for symptomatic relief of PD, as it is an amino acid precursor of dopamine that readily crosses the Blood–Brain Barrier (BBB). However, levodopa exhibits poor plasma bioavailability and limited brain uptake, and induces peripheral side effects. To overcome this biological impediment, we have developed and characterized a lactoferrin-functionalized Pluronic F-127 capped dopamine-loaded mesoporous silica nanocomposite (Lf-DA-MSN-PF127) to furnish dopamine across the BBB. In vivo experiments using a rotenone (ROT) induced PD rat model confirmed that Lf-DA-MSN-PF127 crosses the BBB and delivers dopamine. It remarkably boosts motor symptoms and dopamine levels in ROT-induced PD rats. Our study illustrates the nontoxic effect of the Lf-DA-MSN-PF127 nanocomposite and its efficacy in delivering dopamine across the BBB, providing a novel treatment strategy for PD.

Abstract Image

一种新型纳米复合材料Lf-DA-MSN-PF127在大鼠帕金森病模型中帮助多巴胺的递送。
多巴胺是中枢神经系统的关键神经递质,在运动功能中起重要作用。帕金森病(PD)是一种慢性、进行性、与年龄相关的神经退行性疾病,其特征是中脑黑质致密部多巴胺能神经元的进行性丧失,导致多巴胺水平降低。左旋多巴是缓解帕金森病症状的处方药,因为它是多巴胺的一种氨基酸前体,容易穿过血脑屏障(BBB)。然而,左旋多巴表现出较差的血浆生物利用度和有限的脑吸收,并诱发外周副作用。为了克服这一生物障碍,我们开发并表征了一种乳铁蛋白功能化的Pluronic F-127覆盖的装载多巴胺的介孔二氧化硅纳米复合材料(Lf-DA-MSN-PF127),可以通过血脑屏障提供多巴胺。鱼藤酮(ROT)诱导的PD大鼠体内实验证实,Lf-DA-MSN-PF127穿过血脑屏障并传递多巴胺。它显著提高了rot诱导的PD大鼠的运动症状和多巴胺水平。我们的研究说明了Lf-DA-MSN-PF127纳米复合材料的无毒作用及其在血脑屏障中传递多巴胺的功效,为帕金森病提供了一种新的治疗策略。
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来源期刊
Nanoscale Advances
Nanoscale Advances Multiple-
CiteScore
8.00
自引率
2.10%
发文量
461
审稿时长
9 weeks
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