In vitro sustained release of bioactive anti-NogoA, a molecule in clinical development for treatment of spinal cord injury.
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.
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada.
Jason C
JC
Stanwick
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, 164 College Street, Room 407, Toronto, ON, M5S 3G9, Canada.
M Douglas
MD
Baumann
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada; Institute of Biomaterials and Biomedical Engineering, 164 College Street, Room 407, Toronto, ON, M5S 3G9, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, ON, M5S 3H6, Canada. Electronic address: molly.shoichet@utoronto.ca.
Molly S
MS
Shoichet
D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000627:therapeutic use; D002119:Calcium Carbonate / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying; D006820:Hyaluronic Acid / Q000737:chemistry; D020100:Hydrogels; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry; D008747:Methylcellulose / Q000737:chemistry; D009185:Myelin Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D053758:Nanoparticles; D036103:Nanotechnology; D000070798:Nogo Proteins; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000276:immunology; D013678:Technology, Pharmaceutical / Q000379:methods; D014199:Trehalose / Q000737:chemistry
D000911:Antibodies, Monoclonal; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D020100:Hydrogels; D009185:Myelin Proteins; D000070798:Nogo Proteins; D011108:Polymers; C000603197:Rtn4 protein, rat; C005479:magnesium carbonate; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid; D008747:Methylcellulose; D014199:Trehalose; D002119:Calcium Carbonate; D008274:Magnesium