In vitro and in vivo release of nerve growth factor from biodegradable poly-lactic-co-glycolic-acid microspheres

Ralph De Boer, Andrew M. Knight, Robert J. Spinner, Martijn J A Malessy, Michael J Yaszemski, Anthony John Windebank

Research output: Contribution to journalArticle

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1067-1073
Number of pages7
JournalJournal of Biomedical Materials Research - Part A
Volume95
Issue number4
DOIs
StatePublished - Dec 15 2010

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Keywords

  • dorsal root ganglia
  • microspheres
  • nerve growth factor
  • peripheral nerve
  • poly-lactic-co-glycolic- acid

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Ceramics and Composites
  • Metals and Alloys

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