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Text
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<a href="http://doi.org/10.1208/s12248-017-0176-3" target="_blank" rel="noreferrer noopener">http://doi.org/10.1208/s12248-017-0176-3</a>
Pages
18–18
Issue
1
Volume
20
Dublin Core
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Title
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Therapeutic Delivery of Simvastatin Loaded in PLA-PEG Polymersomes Resulted in Amplification of Anti-inflammatory Effects in Activated Microglia.
Publisher
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The AAPS journal
Date
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2017
2017-12
Subject
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*Drug Delivery Systems; *inflammation; *microglia; *neuroprotection; *polymersomes; *simvastatin; Animals; Anti-Inflammatory Agents/*pharmacology; Inbred BALB C; Interleukin-6/antagonists & inhibitors/biosynthesis; Lactates/*administration & dosage; Mice; Microglia/*drug effects; Nitric Oxide/antagonists & inhibitors/biosynthesis; Polyethylene Glycols/*administration & dosage; Simvastatin/*administration & dosage/pharmacology; Tumor Necrosis Factor-alpha/antagonists & inhibitors/biosynthesis
Creator
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Manickavasagam Dharani; Novak Kimberly; Oyewumi Moses O
Description
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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-alpha) 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.
Identifier
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<a href="http://doi.org/10.1208/s12248-017-0176-3" target="_blank" rel="noreferrer noopener">10.1208/s12248-017-0176-3</a>
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*Drug Delivery Systems
*Inflammation
*Microglia
*neuroprotection
*polymersomes
*simvastatin
2017
Animals
Anti-Inflammatory Agents/*pharmacology
Department of Pharmaceutical Sciences
Inbred BALB C
Interleukin-6/antagonists & inhibitors/biosynthesis
Lactates/*administration & dosage
Manickavasagam Dharani
Mice
Microglia/*drug effects
NEOMED College of Pharmacy
Nitric Oxide/antagonists & inhibitors/biosynthesis
Novak Kimberly
Oyewumi Moses O
Polyethylene Glycols/*administration & dosage
Simvastatin/*administration & dosage/pharmacology
The AAPS journal
Tumor Necrosis Factor-alpha/antagonists & inhibitors/biosynthesis