title: In vitro and in vivo release of nerve growth factor from biodegradable poly-lactic-co-glycolic-acid microspheres.
abstract: Regeneration of peripheral nerves after injury is suboptimal. We now report the long term delivery of nerve growth factor (NGF) by biodegradable poly-lactic-co-glycolic acid (PLGA) microspheres in vitro and in vivo. Lactic to glycolic acid ratios of 50:50 and 85:15 were fabricated using the double emulsion solvent, evaporation technique. Three different inherent viscosities (0.1 dL g(-1) : 1A, 0.4 dL g(-1) : 4A, 0.7 dL g(-1) : 7A) were analyzed. In vitro, release of NGF for 23 days was measured. Electron microscopy demonstrated intact spheres for at least 7 days (50:50 1A), 14 days (50:50 4A), or 35 days (50:50 7A and 85:15 7A). In vitro release kinetics was characterized by burst release, followed by release of NGF at a rate of 0.6-1.6% a day. Release curves for 50:50 1A and 85:15 7A differed significantly from other compositions (p < 0.01). In vivo, release was characterized by a novel radionuclide tracking assay. Release rates varied from 0.9 to 2.2% per day with linear kinetics. All but the 85:15 type of spheres showed different release profiles in vivo compared to in vitro conditions. On the basis of the surface morphology and release profiles, we found microspheres fabricated from 50:50 4A PLGA to be best suited for the use in a rat sciatic nerve injury model.
authors.affiliation: Department of Neurology and Molecular Neuroscience, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: de Boer
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Knight
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Spinner
authors.forename: Martijn J A
authors.initials: MJ
authors.lastname: Malessy
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Windebank
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D001681:Biological Assay; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D019344:Lactic Acid / Q000494:pharmacology*; D008422:Materials Testing; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D020932:Nerve Growth Factor / Q000378:metabolism*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000494:pharmacology*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020932:Nerve Growth Factor