title: Poly(lactic-co-glycolic) acid microspheres encapsulated in Pluronic F-127 prolong hirudin delivery and improve functional recovery from a demyelination lesion.
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.
authors: Department of Neurological Surgery, University of Washington, Seattle, WA 98104, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA. Electronic address: drewfus@uw.edu.
authors: Drew L
authors: DL
authors: Sellers
authors: Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors: Tae Hee
authors: TH
authors: Kim
authors: Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors: Christopher W
authors: CW
authors: Mount
authors: Department of Bioengineering, University of Washington, Seattle, WA, USA.
authors: Suzie H
authors: SH
authors: Pun
authors: Department of Neurological Surgery, University of Washington, Seattle, WA 98104, USA; Neurobiology and Behavior Program, Center on Human Development and Disability, University of Washington, Seattle, Washington, USA; Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA 98195, USA.
authors: Philip J
authors: PJ
authors: Horner
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000008:administration & dosage* / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000737:chemistry*; D003711:Demyelinating Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use; D024764:Hirudin Therapy; D006629:Hirudins / Q000008:administration & dosage*; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D008863:Microspheres; D020442:Poloxamer / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020127:Recovery of Function / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D000991:Antithrombins; D003692:Delayed-Action Preparations; D005343:Fibrinolytic Agents; D006629:Hirudins; D020442:Poloxamer; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006493:Heparin
keywords: Drug release; Hydrogel; Pluronic; Poly(lactic-co-glycolic) acid microspheres; Spinal cord; Thrombin