In vitro sustained release of bioactive anti-NogoA, a molecule in clinical development for treatment of spinal cord injury.
نویسندگان
چکیده
Anti-NogoA is a promising anti-inhibitory molecule that has been shown to enhance functional recovery after spinal cord injury when delivered in rat and primate models over the span of weeks. To achieve this sustained release, anti-NogoA is typically delivered by osmotic minipumps; however, external minipumps are susceptible to infection. To address this issue, we developed a drug delivery system that consists of anti-NogoA-loaded poly(lactic-co-glycolic acid) nanoparticles dispersed in a hydrogel of hyaluronan and methylcellulose (composite HAMC). To optimize in vitro release, we screened formulations for improved anti-NogoA bioactivity and sustained release based on combinations of co-encapsulated trehalose, hyaluronan, MgCO(3), and CaCO(3). Co-encapsulated MgCO(3) and CaCO(3) slowed the rate of anti-NogoA release and did not influence anti-NogoA bioactivity. Co-encapsulated trehalose significantly improved anti-NogoA bioactivity at early release time points by stabilizing the protein during lyophilization. Co-encapsulated trehalose with hyaluronan improved bioactivity up to 28d and dramatically increased the rate and duration of sustained delivery. The sustained release of bioactive anti-NogoA from composite HAMC is a compelling formulation for in vivo evaluation in a model of spinal cord injury.
منابع مشابه
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Tissue and functional repair after spinal cord injury (SCI) continue to elude researchers. Neurotrophin-3 (NT-3) and anti-NogoA have been shown to promote axonal regeneration in animal models of SCI; however, localized and sustained delivery to the central nervous system (CNS) remains a critical challenge for these and other macromolecular therapeutics. An injectable drug delivery system (DDS) ...
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ورودعنوان ژورنال:
- International journal of pharmaceutics
دوره 426 1-2 شماره
صفحات -
تاریخ انتشار 2012