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
International Journal of Pharmaceutics – Elsevier
Published: Apr 15, 2012
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