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Intranasal Administration of TAT-Conjugated Lipid Nanocarriers Loading GDNF for Parkinson’s Disease

文献作者：Sara Hernando, Enara Herran, Joana Figueiro-Silva, José Luis Pedraz, Manoli Igartua, Eva Carro, Rosa Maria Hernandez   《Molecular Neurobiology》

ABSTRACTS
Parkinson’s disease (PD) is the second most common neurodegenerative disorder (ND), characterized by the loss of dopaminergic neurons, microglial activation, and neuroinflammation. Current available treatments in clinical practice cannot halt the progression of the disease. During the last few years, growth factors (GFs) have been raised as a promising therapeutic approach to address the underlying neurodegenerative process. Among others, glial cell-derived neurotrophic factor (GDNF) is a widely studied GF for PD. However, its clinical use is limited due to its short half life, rapid degradation rate, and difficulties in crossing the blood-brain barrier (BBB). Lately, intranasal administration has appeared as an alternative non-invasive way to bypass the BBB and target drugs directly to the central nervous system (CNS). Thus, the aim of this work was to develop a novel nanoformulation to enhance brain targeting in PD through nasal administration. For that purpose, GDNF was encapsulated into chitosan (CS)-coated nanostructured lipid carriers, with the surface modified with transactivator of transcription (TAT) peptide (CS-nanostructured lipid carrier (NLC)-TAT-GDNF). After the physiochemical characterization of nanoparticles, the in vivo study was performed by intranasal administration to a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. The CS-NLC-TAT-GDNF-treated group revealed motor recovery which was confirmed with immunohistochemistry studies, showing the highest number of tyrosine hydroxylase (TH+) fibers in the striatum and TH+ neuron levels in the substantia nigra. Moreover, ionizing calcium-binding adaptor molecule 1 immunohistochemistry was performed, revealing that CS-NLC-TAT-GDNF acts as a modulator on microglia activation, obtaining values similar to control. Therefore, it may be concluded that the intranasal administration of CS-NLC-TAT-GDNF may represent a promising therapy for PD treatment.
KEY WORDS
Parkinson’s disease ;Nanostructured lipid carriers ;Glial derived neurotrophic factor (GDNF) ;TAT peptide ;Neuroprotection.
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TAT was obtained from ChinaPeptides.
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https://link.springer.com/article/10.1007/s12035-017-0728-7
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The therapeutic effect of anti-CD52 treatment in murine experimental autoimmune encephalomyelitis is associated with altered IL-33 and ST2 expression levels

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Mutational analysis of the extracellular disulphide bridges of the atypical chemokine receptor ACKR3/CXCR7 uncovers multiple binding and activation modes for its chemokine and endogenous non-chemokine agonists

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CAS:85466-18-8|Thymopoietin II (32-35)|RKDV

Contact： Liven Qian(钱叶华)-Custom Peptide Mobile: 13761298676（微信） Email：cps037@chinapeptides.net QQ：2880526724 ChinaPeptides Co., Ltd./强耀生物科技有限公司 Name Thymopoietin II (32-35) Code [85466-18-8] The alias Thymopoietin II (32-35) Sequence (single letter abbreviation) RKDV Sequence (three-letter abbreviation) H-Arg-Lys-Asp-Val-OH (trifluoroacetate salt) A basic description TP-4 and TP-3; shortest active thymopoietin II fragments described that exhibit potent immunoregulatory properties in vitro and in vivo. solubility The molecular weight 516.6 Chemical formula C21H40N8O7 The purity 80%，90%，95%，98%，99% Weight 1mg,5mg,10mg,50mg,100mg,1g Storage conditions Store at -20°C. Keep tightly closed. Store in a cool dry place. Number of Residues: 4 1-Letter Code: RKDV 3-Letter Code: Arg-Lys-Asp-Val Molecular weight (Mr): 516.6 g/mol Isoelectric point: 10.1 Net charge at pH 7.0: 1.0 Average hydrophilicity: 1.9 Ratio of hydrophilic residues / total number of residues...
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