Poly(lactic-co-glycolic) acid microspheres encapsulated in Pluronic F-127 prolong hirudin delivery and improve functional recovery from a demyelination lesion

Drew L. Sellers, Tae Hee Kim, Christopher W. Mount, Suzie H. Pun, Philip J. Horner

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Components of the blood have been proposed as potential therapeutic targets for improving cellular regeneration after injury and neurodegenerative disease. In this work, thrombin is shown to increase endogenous neural progenitor proliferation in the intact murine spinal cord. A local injection of heparin before a spinal cord injury reduces cell proliferation and astrogliogenesis associated with scarring. We sought to create depot-formulations of PLGA microsphere and Pluronic F-127 for sustained local delivery of two thrombin inhibitors, heparin and hirudin. Each hydrogel depot-formulation showed delayed drug release compared to microspheres or hydrogel alone. Animals with a lateral demyelination lesion showed a reduction in CD68+ macrophages when treated with hirudin-loaded PLGA/F-127 gels compared to control and heparin-treated animals. Moreover, hirudin-loaded materials showed an accelerated recovery in coordinated stepping and increased oligodendrocyte densities. Together, these data demonstrate that controlled delivery of hirudin accelerates functional recovery from a demyelination lesion in the spinal cord.

Original languageEnglish (US)
Pages (from-to)8895-8902
Number of pages8
JournalBiomaterials
Volume35
Issue number31
DOIs
StatePublished - Oct 2014

Keywords

  • Drug release
  • Hydrogel
  • Pluronic
  • Poly(lactic-co-glycolic) acid microspheres
  • Spinal cord
  • Thrombin

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint Dive into the research topics of 'Poly(lactic-co-glycolic) acid microspheres encapsulated in Pluronic F-127 prolong hirudin delivery and improve functional recovery from a demyelination lesion'. Together they form a unique fingerprint.

Cite this