Local Delivery of Flavopiridol in PLGA Nanoparticles Improves the Repair of Spinal Cord Injury by Inhibiting Astrocyte Growth and Inflammatory Factor Synthesis
首发时间:2014-05-02
Abstract:The cell cycle inhibitor flavopiridol was previously shown in animal models to improve SCI recovery. However, the systematic dosage of flavopiridol is with side effects and the mechanism is not clear. This study aims to develop a strategy for local delivery of flavopiridol and investigate its mechanisms of function as well. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was used for the sustained delivery of flavopiridol. The spinal cords were right-hemisectioned and NPs were administered into the injury site. Transparent spinal cord technology was applied for the three-dimensional observation of the anterograde tracing. The results showed that flavopiridol NPs had a susteined release of up to 3 days in vitro. Flavopiridol NPs significantly decreased inflammatory factor synthesis of astrocytes, including tnf-alpha, il-1beta, and il-6, while the il-10 expression was elevated. In-vivo study demonstrated that flavopiridol NPs decreased inflammatory expression and glial scarring, and facilitated neuronal survival and neural transmitting. Cavitation volume was decreased by proximately 90%. Administration of flavopiridol NPs also improved the motor recovery of injured animals. These findings illustrated that local delivery of flavopiridol in PLGA NPs improved SCI recovery through inhibiting astrocyte growth and inflammatory factor synthesis.
keywords: spinal surgery cell activation nanoparticle astrocyte inflammation drug release
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Local Delivery of Flavopiridol in PLGA Nanoparticles Improves the Repair of Spinal Cord Injury by Inhibiting Astrocyte Growth and Inflammatory Factor Synthesis
摘要:The cell cycle inhibitor flavopiridol was previously shown in animal models to improve SCI recovery. However, the systematic dosage of flavopiridol is with side effects and the mechanism is not clear. This study aims to develop a strategy for local delivery of flavopiridol and investigate its mechanisms of function as well. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was used for the sustained delivery of flavopiridol. The spinal cords were right-hemisectioned and NPs were administered into the injury site. Transparent spinal cord technology was applied for the three-dimensional observation of the anterograde tracing. The results showed that flavopiridol NPs had a susteined release of up to 3 days in vitro. Flavopiridol NPs significantly decreased inflammatory factor synthesis of astrocytes, including tnf-alpha, il-1beta, and il-6, while the il-10 expression was elevated. In-vivo study demonstrated that flavopiridol NPs decreased inflammatory expression and glial scarring, and facilitated neuronal survival and neural transmitting. Cavitation volume was decreased by proximately 90%. Administration of flavopiridol NPs also improved the motor recovery of injured animals. These findings illustrated that local delivery of flavopiridol in PLGA NPs improved SCI recovery through inhibiting astrocyte growth and inflammatory factor synthesis.
关键词: spinal surgery; cell activation; nanoparticle; astrocyte; inflammation; drug release
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Local Delivery of Flavopiridol in PLGA Nanoparticles Improves the Repair of Spinal Cord Injury by Inhibiting Astrocyte Growth and Inflammatory Factor Synthesis
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