期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 426, 期 1-2, 页码 284-290出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2012.01.035
关键词
Anti-NogoA (11c7); Poly(lactic-co-glycolic acid) (PLGA); Nanoparticle; Hydrogel; Drug delivery
资金
- Canadian Institutes of Health Research
- Ontario Graduate Scholarships in Science and Technology
- Natural Sciences and Engineering Research Council of Canada
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, MgCO3, and CaCO3. Co-encapsulated MgCO3 and CaCO3 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. (C) 2012 Elsevier B.V. All rights reserved.
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