John Garner

mPEG-PLA from PolySciTech used in development of nanoparticle treatment to protect brain tissue from inflammation damage

Blog Post created by John Garner on Dec 21, 2017

Manickavasagam, 2017 neuroinflammation.png

One of the major contributing factors to morbidity and death from brain cancer and other neurodegenerative disorders is the inflammation brought on within the brain tissue itself. This leads to swelling, oxidation, and potentially death. Typically treating any ailment that affects the brain is difficult as relatively few medicinal compounds cross from the blood stream into the brain tissue (the blood-brain-barrier). Nanotechnology can be used to improve this however. Recently, researchers at Kent State University and Northeast Ohio Medical University used mPEG-P(DL)La (PolyVivo AK021) from PolySciTech (www.polyscitech.com) to generate a delivery system for simvastatin to protect against neuroinflammation. This research holds promise to reduce damage caused by brain-tumors as well as other diseases implicated with inflammation of neural tissue. Read more: Manickavasagam, Dharani, Kimberly Novak, and Moses O. Oyewumi. "Therapeutic Delivery of Simvastatin Loaded in PLA-PEG Polymersomes Resulted in Amplification of Anti-inflammatory Effects in Activated Microglia." The AAPS Journal 20, no. 1 (2018): 18. https://link.springer.com/article/10.1208/s12248-017-0176-3

  “Abstract: Simvastatin (Sim), a lipid-lowering drug has been studied in chronic neuroinflammation associated with degenerative brain disorders due to its potential protective properties against inflammatory reaction, oxidative damage, neuronal dysfunction, and death. Meanwhile, potential application of Sim in neuroinflammation will require a suitable delivery system that can overcome notable challenges pertaining to poor blood–brain barrier (BBB) permeability and side/off-target effects. Herein, we engineered and characterized nano-sized polymersomes loaded with Sim (Sim-Ps) using PEG-PdLLA (methoxy polyethylene glycol-poly(d,l) lactic acid) diblock co-polymers. Studies in BV2 microglia indicated that Sim-Ps was superior to Sim alone in suppressing nitric oxide (NO) and proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) secretion against LPS activation. The effectiveness of Sim-Ps as compared with Sim alone, in attenuating NO and cytokine production by activated BV2 cells can be attributed to (a) colloidal stability of the delivery platform, (b) protracted release of biologically active Sim, and (c) particulate internalization coupled with enhanced Sim exposure to BV2 cells. Intranasal delivery in BALB/c mice demonstrated enhanced brain distribution with increasing time after administration. Overall data demonstrated suitability of PEG-PdLLA polymersomes in Sim delivery for potential application in treating neuroinflammation. Key Words: inflammation, microglia, neuroprotection, polymersomes, simvastatin”

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