Internalization of particulate delivery systems by activated microglia influenced the therapeutic efficacy of simvastatin repurposing for neuroinflammation
Title
Internalization of particulate delivery systems by activated microglia influenced the therapeutic efficacy of simvastatin repurposing for neuroinflammation
Creator
Manickavasagam Dharani; Oyewumi Moses O
Publisher
International Journal of Pharmaceutics
Date
2019
2019-09
Description
We recently evaluated the suitability of polymersome delivery systems in simvastatin repurposing for treating neuroinflammation. The goal of the current study is to elucidate the therapeutic impact of particulate internalization by activated microglia on the resultant anti-inflammatory properties. Thus, we investigated the endocytic mechanism(s) involved in uptake and transport of simvastatin-loaded polymersomes by BV2 microglia cells coupled with delineation of the intracellular pathway(s) involved in regulating anti-inflammatory effects. Our data indicated that internalization of polymersome delivery systems by activated microglial BV2 cells was important in the suppression of nitric oxide (NO), TNF-α and IL-6 production. Further, we observed that the lipid raft/caveolae pathway had the most influential effect on polymersome internalization by microglia cells while clathrin-mediated endocytosis did not play a major role. Enhancement of anti-inflammatory effects of simvastatin could be attributed to inhibition of ERK1/2, JNK and AKT signaling pathways and internalization of polymersome delivery systems in activated microglia. Taken together, our data provided insights into how the intracellular trafficking of delivery systems by microglial could be a useful tool in modulating the desired anti-inflammatory effects of drugs.
Subject
Brain; Drug delivery; Drug repurposing; PEG-PdLLA; Polymersomes
October 2019 Update
Identifier
Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
URL Address
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Pages
118690-118690
Volume
570
Citation
Manickavasagam Dharani; Oyewumi Moses O, “Internalization of particulate delivery systems by activated microglia influenced the therapeutic efficacy of simvastatin repurposing for neuroinflammation,” NEOMED Bibliography Database, accessed April 24, 2024, https://neomed.omeka.net/items/show/6557.