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Pluronic P85/F68 Micelles of Baicalein Could Interfere with Mitochondria to Overcome MRP2-Mediated Efflux and Offer Improved Anti-Parkinsonian Activity
Chen T.3; Li Y.3; Li C.3; Yi X.1; Wang R.3; Lee S.M.-Y.3; Zheng Y.3
2017-10-02
Source PublicationMolecular Pharmaceutics
ISSN15438392 15438384
Volume14Issue:10Pages:3331-3342
Abstract

Overexpression of the drug efflux transporter multidrug resistance-associated protein 2 (MRP2) in the gastrointestinal tract and blood-brain barrier compromises the oral delivery of drugs to the circulation system and brain in the treatment of Parkinson's disease (PD). In this study, we aim to develop small-sized Pluronic P85/F68 micelles loaded with baicalein (B-MCs) to overcome MRP2-mediated efflux and to investigate related mechanism, as well as the anti-Parkinsonian efficacy. Spherical and sustained-release B-MCs have a mean particle size of 40.61 nm, a low critical micelle concentration (CMC) of 5.01 × 10 mg/mL with an encapsulation efficiency of 95.47% and a drug loading of 7.07%. In comparison with the free baicalein, the cellular uptake and apparent permeability coefficient (P) of B-MCs were significantly enhanced (p < 0.01). Fluorescence resonance energy transfer (FRET) analysis indicated that micelles carrying the hydrophobic fluorophores were internalized intact, followed by a rapid release of fluorophores inside the cells, and then the released free fluorophores were transported across the cell monolayers to the basolateral side. Further study on the MRP2 inhibitory effect showed that B-MCs could reverse the MRP2-mediated efflux of baicalein via interfering with the structure and function of mitochondria, i.e., reducing mitochondrial membrane potential and intracellular ATP level and influencing the respiration chain of mitochondria. In addition, B-MCs exerted strong neuroprotective effects on zebrafish model of PD. In summary, Pluronic P85/F68 micelles could be considered as a promising drug delivery system to reverse MRP2-mediated efflux and improve the bioactivity of this MRP2 substrate, baicalein, for the treatment of PD.

KeywordBaicalein Fluorescence Resonance Energy Transfer (Fret) Micelles Mitochondria Multidrug Resistance-associated Protein 2 (Mrp2) Neuroprotective Effect
DOI10.1021/acs.molpharmaceut.7b00374
URLView the original
Indexed BySCI
WOS Research AreaResearch & Experimental Medicine ; Pharmacology & Pharmacy
WOS SubjectMedicine, Research & Experimental ; Pharmacology & Pharmacy
WOS IDWOS:000412379100010
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Cited Times [WOS]:5   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.The University of North Carolina at Chapel Hill
2.Guangzhou University of Traditional Chinese Medicine
3.University of Macau
First Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Chen T.,Li Y.,Li C.,et al. Pluronic P85/F68 Micelles of Baicalein Could Interfere with Mitochondria to Overcome MRP2-Mediated Efflux and Offer Improved Anti-Parkinsonian Activity[J]. Molecular Pharmaceutics,2017,14(10):3331-3342.
APA Chen T..,Li Y..,Li C..,Yi X..,Wang R..,...&Zheng Y..(2017).Pluronic P85/F68 Micelles of Baicalein Could Interfere with Mitochondria to Overcome MRP2-Mediated Efflux and Offer Improved Anti-Parkinsonian Activity.Molecular Pharmaceutics,14(10),3331-3342.
MLA Chen T.,et al."Pluronic P85/F68 Micelles of Baicalein Could Interfere with Mitochondria to Overcome MRP2-Mediated Efflux and Offer Improved Anti-Parkinsonian Activity".Molecular Pharmaceutics 14.10(2017):3331-3342.
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