Abstract
Purpose:
Intranasal administration of phospholipid-based gelatin nanoparticles (GNP) was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP) on hemiparkinsonian rats.
Methods:
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.
Results:
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.
Conclusions:
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Behavior, Animal / drug effects
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Biomarkers
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Caspase 3 / metabolism
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Cell Line
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Disease Models, Animal
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Dopaminergic Neurons / drug effects*
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Dopaminergic Neurons / metabolism*
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Gelatin / chemistry*
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Male
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Nanoparticles / chemistry*
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Nanoparticles / ultrastructure
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Neurotransmitter Agents / administration & dosage*
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Neurotransmitter Agents / chemistry
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Oxidopamine / adverse effects
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Parkinson Disease / drug therapy
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Parkinson Disease / metabolism
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Parkinson Disease / pathology
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Parkinson Disease / physiopathology
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Proto-Oncogene Proteins c-jun / metabolism
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Rats
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Substance P / administration & dosage*
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Substance P / chemistry
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Tyrosine 3-Monooxygenase / metabolism
Substances
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Biomarkers
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Neurotransmitter Agents
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Proto-Oncogene Proteins c-jun
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Substance P
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Oxidopamine
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Gelatin
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Tyrosine 3-Monooxygenase
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Caspase 3
Grants and funding
This research was supported by National Natural Science Foundation of China (Grant No. 81360195, 81301982, 81571392, 81272160, 81302726 and 81460299); Zhejiang Provincial Foundation for Health Department (Grant No. 2015ZDA023 and 2016139678), Key support of high level talent innovation and technology project of Wenzhou (Ying-Zheng Zhao, 2015); Major Scientific Project of Guangdong Province (Grant No. 2012A080201010); Science and Technology Plan Project of Guangzhou, (201508020001). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.