Incorporation of protein-eluting microspheres into biodegradable nerve guidance channels for controlled release.
Nerve guidance channels (NGCs) promote axonal regeneration after transection injury of the peripheral nerve or spinal cord, yet this regeneration is limited. To enhance regeneration further, we hypothesize that localized delivery of therapeutic molecules combined with the NGC is required. In an attempt to achieve such an NGC, we designed and synthesized a novel NGC in which protein-encapsulated microspheres were stably incorporated into the tube wall. Specifically, poly(lactide-co-glycolide) (PLGA 50/50) microspheres were physically entrapped in the annulus between two concentric tubes, consisting of a chitosan inner tube and a chitin outer tube. Taking advantage of the extensive shrinking that the outer chitin tube undergoes with drying, >15 mg of microspheres were loaded within the tube walls. Using BSA-encapsulated microspheres as the model drug delivery system, BSA was released from microsphere loaded tubes (MLTs) for 84 days, and from freely suspended PLGA microspheres for 70 days. An initial burst release was observed for both MLTs and free microspheres, followed by a degradation-controlled release profile that resulted in a higher release rate from MLTs initially, which was then attenuated likely due to the buffering effect of chitin and chitosan tubes. Epidermal growth factor (EGF), co-encapsulated with BSA in PLGA 50/50 microspheres in MLTs, was released for 56 days with a similar profile to that of BSA. Released EGF was found to be bioactive for at least 14 days as assessed by a neurosphere forming bioassay.
Goraltchouk
Alex
A
Department of Chemical Engineering and Applied Chemistry, University of Toronto 200 College Street, Toronto, ON, Canada M5S 3E5; Institute of Biomaterials and Biomedical Engineering, University of Toronto 4 Taddle Creek Road, Room 407, Toronto, ON, Canada M5S 3G9.
Scanga
Vanessa
V
Department of Surgery, University of Toronto, 1 King's College Circle-1182, Toronto, ON, Canada M5S 1A8.
Morshead
Cindi M
CM
Department of Surgery, University of Toronto, 1 King's College Circle-1182, Toronto, ON, Canada M5S 1A8.
Shoichet
Molly S
MS
Department of Chemical Engineering and Applied Chemistry, University of Toronto 200 College Street, Toronto, ON, Canada M5S 3E5; Department of Chemistry, 80 St. George St., Toronto, ON, Canada M5S 1AH; Institute of Biomaterials and Biomedical Engineering, University of Toronto 4 Taddle Creek Road, Room 407, Toronto, ON, Canada M5S 3G9. Electronic address: molly@ecf.utoronto.ca.
D000465:Algorithms; D002686:Chitin; D048271:Chitosan; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000737:chemistry; D019344:Lactic Acid; D008863:Microspheres; D009416:Nerve Regeneration / Q000187:drug effects*; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011506:Proteins / Q000737:chemistry*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry
D003692:Delayed-Action Preparations; D011108:Polymers; D011506:Proteins; D011994:Recombinant Proteins; D002686:Chitin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid; D004815:Epidermal Growth Factor; D048271:Chitosan