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Oral Delivery of Puerarin Nanocrystals To Improve Brain Accumulation and Anti-Parkinsonian Efficacy
Sha Xiong1; Wei Liu1; Dongli Li1; Xiaojia Chen2; Fang Liu3; Dongsheng Yuan1; Huafeng Pan1; Qi Wang1; Shuhuan Fang1; Tongkai Chen1
2019-04
Source PublicationMOLECULAR PHARMACEUTICS
ISSN1543-8384
Volume16Issue:4Pages:1444-1455
Abstract

Puerarin (PU) has emerged as a promising herb-derived anti-Parkinsonism compound. However, the undesirable water solubility as well as the unwanted bioavailability of PU limit its application. Therefore, this study aimed to develop and characterize PU nanocrystals (PU-NCs) with enhanced oral bioavailability and improved brain accumulation for the treatment of Parkinson's disease (PD). The fabricated PU-NCs were approximately spherical, with a mean size of 83.05 ± 1.96 nm, a PDI of 0.047 ± 0.009, a drug loading of 72.7%, and a rapid dissolution rate in vitro. Molecular dynamics simulation of PU and Pluronic F68 demonstrated the interaction energy and binding energy of -88.1 kJ/mol and -40.201 ± 0.685 kJ/mol, respectively, indicating a spontaneous binding with van der Waals interactions. In addition, the cellular uptake and permeability of PU-NCs were significantly enhanced as compared to PU alone ( p < 0.01). Moreover, PU-NCs exerted a significant neuroprotective effect against the cellular damage induced by the 1-methyl-4-phenylpyridinium ion (MPP+). Besides, PU-NCs demonstrated no obvious toxic effects on zebrafish, as evidenced by the unaltered morphology, hatching, survival rate, body length, and heart rate. Fluorescence resonance energy transfer (FRET) imaging revealed that intact nanocrystals were found in the intestine and brain of adult zebrafish gavaged with DiO/DiI/PU-NCs. Increased values of Cmax and AUC0- t were observed in the plasma of rats following oral administration of PU-NCs compared to PU suspension. Likewise, brain accumulation of PU-NCs was higher than that of PU suspension. Furthermore, PU-NCs attenuated dopamine depletion, ameliorated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced behavioral deficits, and enhanced the levels of dopamine and its metabolites. Taken altogether, this study provides evidence that PU-NCs could be exploited as a potential oral delivery system to treat PD, by improving the poor bioavailability of PU and enhancing their delivery into the brain.

KeywordParkinson’s Disease Brain Accumulation Nanocrystals Oral Delivery Puerarin
DOI10.1021/acs.molpharmaceut.8b01012
Indexed BySCI
Language英语
WOS Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
WOS IDWOS:000463462300003
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Cited Times [WOS]:4   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau,China
3.Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 501405, China
Recommended Citation
GB/T 7714
Sha Xiong,Wei Liu,Dongli Li,et al. Oral Delivery of Puerarin Nanocrystals To Improve Brain Accumulation and Anti-Parkinsonian Efficacy[J]. MOLECULAR PHARMACEUTICS,2019,16(4):1444-1455.
APA Sha Xiong.,Wei Liu.,Dongli Li.,Xiaojia Chen.,Fang Liu.,...&Tongkai Chen.(2019).Oral Delivery of Puerarin Nanocrystals To Improve Brain Accumulation and Anti-Parkinsonian Efficacy.MOLECULAR PHARMACEUTICS,16(4),1444-1455.
MLA Sha Xiong,et al."Oral Delivery of Puerarin Nanocrystals To Improve Brain Accumulation and Anti-Parkinsonian Efficacy".MOLECULAR PHARMACEUTICS 16.4(2019):1444-1455.
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