Small-sized mPEG-PLGA nanoparticles of schisantherin A with sustained release for enhanced brain uptake and anti-Parkinsonian activity.
Abstract
Schisantherin A (SA) is a promising anti-Parkinsonism natural product. However, its poor water solubility and rapid serum clearance impose significant barriers to delivery of SA to the brain. This work aimed to develop SA in a nanoparticle formulation that extended SA circulation in the bloodstream and consequently an increased brain uptake and thus to be potentially efficacious for the treatment of Parkinson’s disease (PD). Spherical SA nanoparticles with a mean particle size of 70 nm were prepared by encapsulating SA into methoxy poly(ethylene glycol)- block -poly( d, l )-lactic- co -glycolic acid (mPEG–PLGA) nanoparticles (SA-NPs) with an encapsulation efficiency of ∼91% and drug loading of ∼28%. The in vitro release of the SA-NPs lasted for 48 h with a sustained-release pattern. Using the Madin–Darby canine kidney (MDCK) cell model, the results showed that first intact nanoparticles carrying hydrophobic dyes were internalized into cells, then the dyes were slowly released within the cells, and last both nanoparticles and free dyes were externalized to the basolateral side of the cell monolayer. Fluorescence resonance energy transfer (FRET) imaging in zebrafish suggested that nanoparticles were gradually dissociated in vivo with time, and nanoparticles maintained intact in the intestine and brain at 2 h post-treatment. When SA-NPs were orally administrated to rats, much higher C max and AUC 0-t were observed in the plasma than those of the SA suspension. Furthermore, brain delivery of SA was much more effective with SA-NPs than with SA suspension. In addition, the SA-NPs exerted strong neuroprotective effects in zebrafish and cell culture models of PD. The protective effect was partially mediated by the activation of the protein kinase B (Akt)/glycogen synthase kinase-3β (Gsk3β) pathway. In summary, this study provides evidence that small-sized mPEG–PLGA nanoparticles may improve cross-barrier transportation, oral bioavailability, brain uptake, and bioactivity of this Biopharmaceutics Classification System (BCS) Class II compound, SA.
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Schisantherin A nanoparticles exert strong neuroprotective effects in zebrafish and cell culture models of Parkinson disease.
“In addition, the SA-NPs exerted strong neuroprotective effects in zebrafish and cell culture model of PD”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Chen et al., 2017
Nanoparticulate delivery of Schisantherin A is much more effective than Schisantherin A suspension alone.
“It was found that nanoparticulate delivery of SA was much more effective than SA suspension alone.”
From Nanotechnology: A Promising Approach for Delivery of Neuroprotective Drugs (2020) · cites this paper as Chen et al., 2017
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- Authors
- Chen, T., Li, C., Li, Y., Yi, X., Wang, R., Lee, S. M.-Y., & Zheng, Y.
- Affiliations
- University of Macau (MO)
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Zheng, Ying
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-03-09
- Volume
- 9
- Issue
- 11
- Pages
- 9516-9527
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W2592553712
- Cited by
- 89
- References
- 46
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 6 · 2023: 16 · 2022: 10 · 2021: 7 · 2020: 15 · 2019: 13 · 2018: 6 · 2017: 4
- FWCI
- 3.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundo para o Desenvolvimento das Ci?ncias e da Tecnologia (112/2013/A3)
- Fundo de Investiga??o, Universidade de Macau (MYRG112(Y1-L3)-ICMS13-ZY)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- schisantherin A, Parkinson's disease, brain drug delivery, sustained drug release, oral bioavailability, nanoparticle uptake, neuroprotection, Akt/GSK-3β signaling, nanoparticle formulation
- MeSH terms
- Animals, Brain, Delayed-Action Preparations, Dioxoles, Dogs, Drug Carriers, Particle Size, Polyesters, Polyethylene Glycols, Lignans, Cyclooctanes, Rats, Nanoparticles
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