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Cited by 260

The DOI matches its Crossref record; 80 of the 80 references it cites were found in a registry or an index.

Trans-Blood Brain Barrier Delivery of Dopamine-Loaded Nanoparticles Reverses Functional Deficits in Parkinsonian Rats

Open access
Pahuja, Richa, Seth, Kavita, Shukla, Anshi, Shukla, Rajendra Kumar, Bhatnagar, Priyanka, Chauhan, Lalit Kumar Singh, Saxena, Prem Narain, Arun, Jharna, Chaudhari, Bhushan Pradosh, Patel, Devendra Kumar, Singh, Sheelendra Pratap, Shukla, Rakesh, Khanna, Vinay Kumar, Kumar, Pradeep, Chaturvedi, Rajnish Kumar, Gupta, Kailash Chand·2015·ACS Nano
DOI 10.1021/nn506408v
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Abstract

Sustained and safe delivery of dopamine across the blood brain barrier (BBB) is a major hurdle for successful therapy in Parkinson's disease (PD), a neurodegenerative disorder. Therefore, in the present study we designed neurotransmitter dopamine-loaded PLGA nanoparticles (DA NPs) to deliver dopamine to the brain. These nanoparticles slowly and constantly released dopamine, showed reduced clearance of dopamine in plasma, reduced quinone adduct formation, and decreased dopamine autoxidation. DA NPs were internalized in dopaminergic SH-SY5Y cells and dopaminergic neurons in the substantia nigra and striatum, regions affected in PD. Treatment with DA NPs did not cause reduction in cell viability and morphological deterioration in SH-SY5Y, as compared to bulk dopamine-treated cells, which showed reduced viability. Herein, we report that these NPs were able to cross the BBB and capillary endothelium in the striatum and substantia nigra in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Systemic intravenous administration of DA NPs caused significantly increased levels of dopamine and its metabolites and reduced dopamine-D2 receptor supersensitivity in the striatum of parkinsonian rats. Further, DA NPs significantly recovered neurobehavioral abnormalities in 6-OHDA-induced parkinsonian rats. Dopamine delivered through NPs did not cause additional generation of ROS, dopaminergic neuron degeneration, and ultrastructural changes in the striatum and substantia nigra as compared to 6-OHDA-lesioned rats. Interestingly, dopamine delivery through nanoformulation neither caused alterations in the heart rate and blood pressure nor showed any abrupt pathological change in the brain and other peripheral organs. These results suggest that NPs delivered dopamine into the brain, reduced dopamine autoxidation-mediated toxicity, and ultimately reversed neurochemical and neurobehavioral deficits in parkinsonian rats.

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Metadata

Authors
Pahuja, R., Seth, K., Shukla, A., Shukla, R. K., Bhatnagar, P., Chauhan, L. K. S., Saxena, P. N., Arun, J., Chaudhari, B. P., Patel, D. K., Singh, S. P., Shukla, R., Khanna, V. K., Kumar, P., Chaturvedi, R. K., & Gupta, K. C.
Venue
ACS Nano
Publisher
American Chemical Society (ACS)
Published
2015-04-22
Volume
9
Issue
5
Pages
4850-4871
ISSN
  • 1936-0851 (ISSN-L)
  • 1936-086X
DOI
10.1021/nn506408v
OpenAlex
W2043737083
Cited by
260
References
80
FWCI
6.41
Type
journal article
Language
en
Open access
hybrid

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