Wednesday, March 15, 2017

Parkinson’s disease treatment developed using mPEG-PLGA block copolymer for neuroprotective agent delivery

Parkinson’s disease is a chronic, neural-degenerative which affects motor control and other operations of the nervous system eventually leading to death. Schisantherin A is a recently discovered neuroprotective agent which acts to inhibit damage to neural cells and can be used to slow the progression of Parkinson’s disease (https://www.ncbi.nlm.nih.gov/pubmed/25770828). It has severe limitations, however, as it is poorly soluble in water and quickly cleared from the blood-stream.  Schisantherin A , like many neurological medicines, also faces the severe impediment of the blood-brain-barrier. This barrier which exists between circulating blood and brain tissue is intended to protect the brain from any toxic components that may be in the blood but also serves the unintentional purpose of preventing uptake of medicinal components into the brain tissue.  Recently, researchers at University of North Carolina at Chapel Hill and University of Macau utilized mPEG-PLGA to generate small-sized nanoparticles containing Schisantherin A. They found these nanoparticles to improve serum circulation longevity and uptake across the blood-brain-barrier. This research holds promise for enhanced therapy against this fatal disease. Similar block copolymers can be purchased from PolySciTech division of Akina, Inc. (www.polyscitech.com). Read more about this exciting research here: Chen, Tongkai, Chuwen Li, Ye Li, Xiang Yi, Ruibing Wang, Simon Ming-Yuen Lee, and Ying Zheng. "Small-Sized mPEG–PLGA Nanoparticles of Schisantherin A with Sustained Release for Enhanced Brain Uptake and Anti-Parkinsonian Activity." ACS Applied Materials & Interfaces (2017). http://pubs.acs.org/doi/abs/10.1021/acsami.7b01171

“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 Cmax and AUC0-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. Keywords: brain delivery; cellular uptake; fluorescence resonance energy transfer (FRET); mPEG−PLGA nanoparticles; oral bioavailability; Schisantherin A”


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