In vitro sustained release of bioactive anti-NogoA, a molecule in clinical development for treatment of spinal cord injury

In vitro sustained release of bioactive anti-NogoA, a molecule in clinical development for... Article history: Anti-NogoA is a promising anti-inhibitory molecule that has been shown to enhance functional recov- Received 29 July 2011 ery after spinal cord injury when delivered in rat and primate models over the span of weeks. To Received in revised form 6 January 2012 achieve this sustained release, anti-NogoA is typically delivered by osmotic minipumps; however, exter- Accepted 15 January 2012 nal minipumps are susceptible to infection. To address this issue, we developed a drug delivery system Available online 24 January 2012 that consists of anti-NogoA-loaded poly(lactic-co-glycolic acid) nanoparticles dispersed in a hydro- gel of hyaluronan and methylcellulose (composite HAMC). To optimize in vitro release, we screened Keywords: formulations for improved anti-NogoA bioactivity and sustained release based on combinations of co- Anti-NogoA (11c7) encapsulated trehalose, hyaluronan, MgCO , and CaCO . Co-encapsulated MgCO and CaCO slowed the 3 3 3 3 Poly(lactic-co-glycolic acid) (PLGA) rate of anti-NogoA release and did not influence anti-NogoA bioactivity. Co-encapsulated trehalose sig- Nanoparticle nificantly improved anti-NogoA bioactivity at early release time points by stabilizing the protein during Hydrogel Drug delivery lyophilization. Co-encapsulated trehalose with hyaluronan improved bioactivity up to 28 d and dramati- cally increased the rate and duration of sustained delivery. The http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png International Journal of Pharmaceutics Elsevier

In vitro sustained release of bioactive anti-NogoA, a molecule in clinical development for treatment of spinal cord injury

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Publisher
Elsevier
Copyright
Copyright © 2012 Elsevier B.V.
ISSN
0378-5173
D.O.I.
10.1016/j.ijpharm.2012.01.035
Publisher site
See Article on Publisher Site

Abstract

Article history: Anti-NogoA is a promising anti-inhibitory molecule that has been shown to enhance functional recov- Received 29 July 2011 ery after spinal cord injury when delivered in rat and primate models over the span of weeks. To Received in revised form 6 January 2012 achieve this sustained release, anti-NogoA is typically delivered by osmotic minipumps; however, exter- Accepted 15 January 2012 nal minipumps are susceptible to infection. To address this issue, we developed a drug delivery system Available online 24 January 2012 that consists of anti-NogoA-loaded poly(lactic-co-glycolic acid) nanoparticles dispersed in a hydro- gel of hyaluronan and methylcellulose (composite HAMC). To optimize in vitro release, we screened Keywords: formulations for improved anti-NogoA bioactivity and sustained release based on combinations of co- Anti-NogoA (11c7) encapsulated trehalose, hyaluronan, MgCO , and CaCO . Co-encapsulated MgCO and CaCO slowed the 3 3 3 3 Poly(lactic-co-glycolic acid) (PLGA) rate of anti-NogoA release and did not influence anti-NogoA bioactivity. Co-encapsulated trehalose sig- Nanoparticle nificantly improved anti-NogoA bioactivity at early release time points by stabilizing the protein during Hydrogel Drug delivery lyophilization. Co-encapsulated trehalose with hyaluronan improved bioactivity up to 28 d and dramati- cally increased the rate and duration of sustained delivery. The

Journal

International Journal of PharmaceuticsElsevier

Published: Apr 15, 2012

References

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