title: A novel polymeric drug delivery system for localized and sustained release of tacrolimus (FK506).
abstract: Despite substantial improvement in microsurgical techniques for nerve repair, recovery after peripheral nerve injury is usually incomplete. FK506, an FDA approved immunosuppressant, improves functional recovery and reinnervation following peripheral nerve injury in animal models. However, systemically delivered FK506 causes undesirable global immunosuppression. We have, therefore, engineered a biodegradable local delivery system for FK506 using fibrin gel as a drug reservoir that could be placed at a site of nerve injury. FK506 was incorporated into fibrin gel in solubilized, particulated, and poly(lactic-co-glycolic) acid (PLGA) microspheres-encapsulated forms. A tunable release of FK506 in the fibrin gel from days to weeks was observed with the rate of release being most rapid for the solubilized form and then the particulate form. The most prolonged period of release was seen with the PLGA microsphere-encapsulated form. As analyzed by in vitro dorsal root ganglion (DRG) neurite extension assay, PLGA microsphere encapsulation of FK506 did not alter the drug's properties and the released FK506 maintained its bioactivity over the entire period of release. This study suggests that local delivery of FK506 with fibrin hydrogel could be used to enhance peripheral nerve regeneration.
authors: Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada, M5G1X8. kasra.tajdaran@mail.utoronto.ca.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. kasra.tajdaran@mail.utoronto.ca.
authors: Kasra
authors: K
authors: Tajdaran
authors: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.|Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
authors: Molly S
authors: MS
authors: Shoichet
authors: Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada, M5G1X8.|Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.|Program in Neuroscience, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors: Tessa
authors: T
authors: Gordon
authors: Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario, Canada, M5G1X8.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.|Division of Plastic and Reconstructive Surgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.|Program in Neuroscience, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors: Gregory H
authors: GH
authors: Borschel
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005337:Fibrin / Q000737:chemistry*; D005727:Ganglia, Spinal / Q000166:cytology; D019344:Lactic Acid / Q000737:chemistry*; D016501:Neurites / Q000187:drug effects; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D044968:Regenerative Medicine; D016559:Tacrolimus / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D005337:Fibrin; D016559:Tacrolimus
keywords: FK506; drug delivery; fibrinogen; nerve injury; poly(lactic-co-glycolic) acid; regenerative medicine