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Abstract Title:

Nanoparticles Mediating the Sustained Puerarin Release Facilitate Improved Brain Delivery to Treat Parkinson's Disease.

Abstract Source:

ACS Appl Mater Interfaces. 2019 Dec 4 ;11(48):45276-45289. Epub 2019 Oct 29. PMID: 31638771

Abstract Author(s):

Tongkai Chen, Wei Liu, Sha Xiong, Dongli Li, Shuhuan Fang, Zhenfeng Wu, Qi Wang, Xiaojia Chen

Article Affiliation:

Tongkai Chen

Abstract:

Recent work has highlighted the potential of puerarin (PU) as a valuable compound to treat Parkinson's disease (PD), but its undesirable water solubility and bioavailability have constrained its utility. In this study, we sought to develop nanoparticles (NPs) that could be used to encapsulate PU, thereby extending its in vivo half-life and improving its bioavailability and accumulation in the brain to treat the symptoms of PD. We prepared spherical NPs (88.36± 1.67 nm) from six-armed star-shaped poly(lactide--glycolide) (6-s-PLGA) NPs that were used to encapsulate PU (PU-NPs) with 89.52± 1.74% encapsulation efficiency, 42.97 ± 1.58% drug loading, and a 48 h sustained drug release. NP formation and drug loading were largely mediated by hydrophobic interactions, while changes in the external environment led these NPs to become increasingly hydrophilic, thereby leading to drug release. Relative to PU alone, PU-NPs exhibited significantly improved cellular internalization, permeation, and neuroprotective effects. Upon the basis of Förster resonance energy transfer (FRET) of NPs-administered zebrafish, we were able to determine that these NPs were rapidly absorbed into circulation whereupon they were able to access the brain. We further conducted oral PU-NPs administration to rats, revealing significant improvements in PU accumulation within the plasma and brain relative to rats administered free PU. In MPTP-mediated neurotoxicity in mice, we found that PU-NPs treatmentimproved disease-associated behavioral deficits and depletion of dopamine and its metabolites. These findings indicated that PU-NPs represent a potentially viable approach to enhancing PU oral absorption, thus improving its delivery to the brain wherein it can aid in the treatment of PD.

Study Type : Animal Study

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